Interactions between ferroptosis and tumour development mechanisms: Implications for gynaecological cancer therapy (Review)
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- Published online on: December 5, 2024 https://doi.org/10.3892/or.2024.8851
- Article Number: 18
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Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Abstract
Introduction
The high incidence of gynaecological malignancies threatens women's health and longevity. Depending on their origin, gynaecological malignancies are often categorized individually, and they present different risk factors, symptoms, growth predictions and treatments (1). As the leading cause of cancer death in women, breast cancer (BCa) remains a global public health problem (2). Cervical cancer is second after BCa and causes >300,000 deaths per year (3). The low 5-year survival rate (4–6) of ovarian cancer (OC) is because most patients are at the terminal stage when they are diagnosed, and some exhibit chemoresistance (7). In addition to the ovary and cervix, the endometrium may also be affected by malignant tumours. The development of endometrial cancer is mainly influenced by metabolic imbalance and genetic susceptibility (8,9). The main treatment options for gynaecological malignancies are surgery, chemotherapy and radiotherapy. Chemotherapy aims to induce apoptosis in tumour cells, selectively eliminating cancer cells without harming normal cells, but some patients develop escape from apoptosis and chemotherapy resistance. Regulatory cell death (RCD) can be modulated by pharmacological or genetic interventions and is controlled by specific signalling pathways. Exploring nonapoptotic RCD processes may provide another strategy for breaking through the antiapoptotic characteristics of tumours to inhibit tumour growth.
The discovery of ferroptosis stems from the 2003 appearance of erastin (10), a compound with selective lethal effects on RAS-expressing cancer cells with different cell death patterns. In 2012, Dixon et al (11) named the process ferroptosis on the basis of its death characteristics. Iron accumulation catalyses the oxidation of phospholipids with polyunsaturated fatty acid (PUFA) residues through the Fenton reaction (5), leading to an imbalance of oxidative and antioxidant systems and resulting in lipid peroxidation (12) and the formation of lipid ROS, which ultimately rupture the cell membrane and then lead to programmed cell death (6). There have been substantial breakthroughs in the research of ferroptosis in cancer. Cancer cells can mediate ferroptosis resistance through related signalling pathways (13) and tumour factors, which are conducive to occurrence, development, metastasis and treatment resistance (14). A high reactive oxygen species (ROS) load makes tumour cells vulnerable to ferroptosis treatment (15). Ferroptosis has been shown to be associated with a variety of gynaecological cancers (16), such as breast, cervical, ovarian and endometrial cancer. However, the potential importance of ferroptosis in the treatment of gynaecological malignancies has not been fully explored.
The vigorous metabolism and rapid proliferation of tumour cells cause a hypoxic tumour microenvironment (TME). Cancer cells undergo changes in signalling pathways and molecular expression to adapt to the hypoxic environment and escape immune surveillance, and hypoxia affects tumour biological behaviour and treatment effects (17). Hypoxia inducible factor (HIF) is the main regulator of the hypoxic microenvironment (18). It is activated under hypoxic conditions, and it promotes tumour angiogenesis, regulates metabolic reprogramming, and increases chemoradiotherapy resistance (19). Hypoxia directly affects the expression of ferroptosis-related molecules, upregulates the expression of iron oxidase and stearoyl-CoA desaturase 1 (SCD1), downregulates iron autophagy-related protein nuclear receptor coactivator 4 (NCOA4), limits intracellular Fe2+, and inhibits ferroptosis (20). Moreover, HIF and nuclear factor erythroid 2-related factor 2 (Nrf2) are involved in regulating and coordinating the antioxidant mechanisms of ferroptosis and iron homeostasis (21). HIF-1 increases the transcription of SLC7A11 and HO-1, inhibiting ferroptosis (22). Hypoxia increases Nrf2 activity, increases HO-1 expression, and inhibits ferroptosis (23,24). Inflammatory molecules released by cancer cells (such as IL-8, CXCL1 and CTSC) and cells in the TME, such as cancer-associated fibroblasts, can induce neutrophil extracellular trap (NET) formation, and cancer cells in a hypoxic environment may have an increased ability to induce NETs (25). Hypoxia-activated HIF-1α promotes M2 macrophage polarization by increasing the expression of VEGF, Arg1 and other M2-related genes (26). Hypoxia also affects mitochondrial behaviour, inducing the production of mitochondrial ROS (mtROS) through mitochondrial complex I dysfunction and the activation of the mitochondrial Na+/Ca2+ exchanger NCLX (27). The increase in mtROS induces mitochondrial autophagy, which is related to the mTOR/AKT/HIF1α signalling axis (28), further improving the oxygen tolerance of cancer cells (29). Ferredoxin 1 (FDX1) and protein acylation are key regulators of cuproptosis. Tumour hypoxia significantly downregulates the expression of FDX1 in cells, thereby significantly inhibiting cuproptosis (30). Tumour cells are highly adaptable in hypoxic microenvironments; have heightened resistance to adverse factors such as ferroptosis and cuproptosis; and promote proliferation, oxygen resistance and invasion by inducing macrophages to polarize to M2 (protumour type), increasing NET release, and activating mitochondrial autophagy (Fig. 1).
To date, the intrinsic network between ferroptosis and other tumour-related mechanisms has not been fully characterized. Therefore, the latest research progress on the crosstalk between ferroptosis and macrophage polarization, NETs, mitochondrial autophagy and cuproptosis is reviewed. The role of ferroptosis in female cancers has gradually emerged in recent years. In the present review, research advances in the field of ferroptosis in gynaecological malignancies and the implications for gynaecological cancer therapy are discussed.
Overview of ferroptosis
Ferroptosis is a special type of regulated cell death characterized by intracellular iron overload, with excessive accumulation of lipid peroxides on the cell membrane damaging membrane integrity. It occurs when the ferroptosis defence mechanism is out of balance (Fig. 2). Thus, lipid peroxidation, iron metabolism and the anti-ferroptosis system constitute the cornerstones of ferroptosis; conversely, ferroptosis can be induced or inhibited by genetic or pharmacological intervention in these three aspects.
Lipid peroxidation
Polyunsaturated fatty acids (PUFAs), which are produced from food, acetyl-CoA carboxylase (ACC), or lipid phagocytes, are indispensable substrates for lipid peroxidation under iron overload conditions. They bind with specific membrane phospholipids (PLs) to form PUFA-PLs (12). Acyl-CoA synthetase long-chain family member 4 (ACSL4) and lysolipid phosphatidylcholine acyltransferase 3 (LPCAT3) are crucial drivers of ferroptosis (31,32). ACSL4 attaches long-chain PUFAs to CoA, catalysing the conversion of free PUFAs to acyl-CoA derivatives (PUFA-CoAs) (33). The latter are further incorporated into membrane phospholipids by LPCAT3 and possibly other enzymes, such as AGPAT3, increasing the amount of long-chain PUFAs in cellular lipids and membranes. Lipid peroxides interact with Fe2+ to produce peroxide radicals, which extract hydrogen from adjacent acyl chains in the lipid membrane, propagating the lipid peroxidation process. This process is mediated by lipoxygenases (ALOXs) or cytochrome P450 oxidoreductases (34). The products of lipid peroxidation include initial lipid hydroperoxides (LOOHs) and subsequent reactive aldehydes such as malondialdehyde (MDA). The accumulation of lipid peroxides leads to membrane damage and instability, eventually resulting in cell death.
Iron accumulation
Iron metabolism is a static and dynamic regulatory process involving the absorption, storage, utilization and excretion of iron and the participation of numerous proteins and molecules. Iron absorption occurs mainly in the duodenum and upper jejunum, and dietary iron is absorbed in the form of Fe2+. Non-haem iron in food is mainly in the form of insoluble Fe3+, which binds to transferrin (TF) in serum and is subsequently recognized by the TF receptor (TFRC) on cell membranes (35). TF carrying Fe3+ binds to TFR1 to form a complex that is internalized into the endosome. In endosomes, prostate epithelial antigen 3 reduces Fe3+ to Fe2+, which is then transported by ZIP8/14 (zinc transporter 8/14) or divalent metal transporter 1 (DMT1), thus promoting the formation of labile iron pools (LIP) (36). In addition to extracellular iron transport, LIP expansion can be facilitated by haem degradation and ferritinophagy mediated by NCOA4 (37), which can be excreted from cells via the lysosome DMT1 (38). The iron in a cell's LIP can be used in the mitochondria, sequenced in ferritin, or excreted from the cell via ferritransporter (FPN). Iron plays a key role in the induction and propagation of lipid peroxidation, possibly by increasing the activity of ALOX or EGLN prolyl hydroxylase and promoting free radical production, which leads to lipid peroxidation and cell membrane damage, causing an imbalance of enzyme-regulated lipid peroxidation and oxygen homeostasis. In iron-overloaded cells, iron is released from these compartments and increases the intracytoplasmic iron concentration (39), thus promoting the Fenton reaction and enhancing cell ROS production.
Core pathway of anti-ferroptosis effects
The glutathione peroxidase 4 (GPX4)-glutathione (GSH) axis represents a pivotal pathway in countering ferroptosis. GPX4 effectively combats lipid peroxidation by utilizing GSH as a reducing agent. The synthesis of GSH relies on cystine, whose uptake is mediated by the cystine reverse transport system Xc-. This system comprises solute carrier family 7 member 11 (SLC7A11) and solute carrier family 7 member 11 (SLC3A2). The proteins encoded by the SLC7A11 and SLC3A2 genes form a transmembrane transporter that is responsible for importing cystine into cells, where it is then used to synthesize GSH. With GSH as a cofactor, GPX4 reduces LOOHs to lipid alcohols, protecting cells from the threat of ferroptosis. Additionally, nicotinamide adenine dinucleotide phosphate (NADPH) plays a vital role in the GPX4-GSH axis (11). As an electron donor, NADPH participates in the recycling of GSH, enabling it to continuously exert its antioxidant effects. Any disturbance to the GPX4-GSH axis may trigger excessive generation of ROS, leading to the occurrence of lipid peroxidation. These disturbances include the degradation of GPX4 through autophagy or the ubiquitin-proteasome system (40); the inhibition of system Xc- by drugs such as erastin and sorafenib; the direct inhibition of GPX4 by drugs such as RAS-synthetic lethal 3 (RSL3) and the nitro-isoxazole-containing compound (ML210); or defects in GSH, cysteine, or NADPH (41). Previously, scientists discovered a ferroptosis inhibition mechanism that is independent of the GPX4 antioxidant pathway (42). The FSP1-CoQ10-NAD(P)H system, which acts in parallel and independently, synergizes with GPX4 and glutathione to inhibit phospholipid peroxidation and ferroptosis. As a powerful ferroptosis inhibitor, FSP1 (ferroptosis suppressor protein 1) (43) exerts antioxidant effects via coenzyme Q10 (CoQ10) with NADPH to regenerate reduced CoQ10 (CoQ10H2). In the mitochondrial lipid protection system, dihydrolactate dehydrogenase (DHODH), an enzyme located on the outer surface of the inner mitochondrial membrane, is essential. It oxidizes dihydrolactate (DHO) to lactate (OA) in the inner mitochondrial membrane and simultaneously reduces CoQ to CoQH2 (44,45). Therefore, DHODH/CoQ can protect mitochondria from oxidative damage (46). Furthermore, GTP cyclohydrolase 1 plays a significant role in this antioxidant system. It produces tetrahydrobiopterin (BH4), which can capture lipid-derived peroxyl radicals and reduce oxidized lipids. Simultaneously, BH4 contributes to the production of CoQ10H2, further enhancing the resistance of cells to oxidative stress and ferroptosis (47). In summary, the combined dysregulation of iron metabolism and the redox system leads to the accumulation of LOOHs in cells, ultimately triggering ferroptosis. The GPX4-GSH axis and other related mechanisms play crucial roles in this life-and-death struggle, jointly maintaining cellular homeostasis and survival.
Inducers and inhibitors of ferroptosis
Ferroptosis is a regulated mode of cell death that can be induced or inhibited by targeting iron metabolism, lipid metabolism and the antioxidant system (GSH/GPX4 axis, CoQ/FSP1) (11,48–50). Erastin induces cell death in an iron-dependent manner. It targets voltage-dependent anion channels (VDACs) and binds to VDAC2, inducing lipid ROS production and mitochondrial dysfunction (48). RSL5 (49), which binds to VDAC3, acts similarly on VDACs. Additionally, diisothiocyanatostilbene-2′,2-disulfonic acid (DIDS) (50) can block VDACs and inhibit DNA damage repair, thereby inducing ferroptosis. Temozolomide (TMZ) can disrupt intracellular iron levels and iron homeostasis by enhancing DMT1 (51), thereby inducing ferroptosis (52). MMRi62, a small-molecule quinolinol, induces the degradation of the ferritin heavy chain, disrupting intracellular iron homeostasis and leading to the accumulation of iron ions within cells and an increase in ROS, which ultimately induces ferroptosis (53). Ferroptosis is closely related to lipid metabolism, and disrupting lipid metabolism can also regulate ferroptosis. Sorafenib (54) is an antitumour drug, and the expression level of ACSL4 is associated with cellular sensitivity to sorafenib. The addition of sorafenib directly affects the metabolic pathway of lipid ROS generation in cells, leading to oxidative stress and DNA damage, which ultimately induces ferroptosis. The small-molecule compound tert-butyl hydroperoxide (55) can directly affect lipid ROS levels, causing abnormalities in the mitochondrial membrane potential and inducing ferroptosis. By targeting the GSH-GPX4 axis, multiple steps can be regulated. RSL3, ML162, diphenyleneiodonium (DPI) and ferroptosis-inducing 56 (FIN56) can induce ferroptosis by promoting the degradation of GPX4 (56,57). In addition to blocking VDAC, erastin depletes GSH to further weaken the antioxidant capacity of cells, simultaneously inducing GPX4 degradation, exacerbating lipid peroxidation, and inducing ferroptosis (58). By targeting the FSP1/CoQ-related pathway, NDP4928 binds and inhibits FSP1, enhancing the GSH-induced suppression of ferroptosis (59). FIN56 inhibits farnesyl diphosphate farnesyltransferase (SQS), reduces cholesterol synthesis, depletes CoQ, degrades GPX4, causes mitochondrial dysfunction, and promotes the induction of ferroptosis. Different compounds target different steps of the GSH-GPX4 axis, including promoting GPX4 degradation, depleting GSH, and inhibiting FSP1 and SQS, to induce ferroptosis through multiple mechanisms. The emergence of ferroptosis inhibitors has also advanced research on the regulation of ferroptosis. For example, cyclopyrrolone (11), deferoxamine, deferiprone and deferasirox (60) inhibit ferroptosis by chelating iron ions, whereas ferrostatin-1 (Fer-1) inhibits lipid peroxidation induced by aromatic amines. microRNA-522 inhibits ferroptosis by targeting arachidonate ALOX15 (61). β-ME helps to produce cystine, increases GPX4 expression, and inhibits ferroptosis by reacting with cystine to form mixed disulphide bonds (62). 2-Cyano-3,12-dioxooleana-1,9 (11)-dien-28-oic acid inhibits the function of heat shock protein (HSP) 90, thereby inhibiting the degradation of GPX4 and protecting cells from ferroptosis (58). These findings provide new strategies and ideas for cancer treatment, and they offer important clues for elucidating the regulatory network of ferroptosis and developing new anticancer strategies.
Ferroptosis and macrophage polarization
Macrophages can adopt distinct phenotypes (63), becoming M1 and M2 macrophages, in response to environmental stimuli in the TME (64). M1 macrophages typically suppress tumour growth by promoting inflammation and antibacterial activity. To promote antitumour immune responses, they can secrete proinflammatory cytokines such as IL-12 and TNF-α, attracting CD8+ T cells as well as NK cells (65). M2 macrophages promote angiogenesis and produce growth factors such as TGF-β, which facilitate tumour cell proliferation and survival (66,67). Iron is an essential trace element for cellular proliferation and division and participates in various biological processes, including DNA synthesis and energy metabolism. Iron metabolism plays a crucial role in macrophage polarization and is linked to immunogenic cell death in tumour cells, thus potentially influencing the M1/M2 macrophage balance and consequently tumour growth and progression (68–70). M1 macrophages typically exhibit high levels of iron storage and low levels of iron release (71), whereas M2 macrophages display the opposite pattern. The activation of ferroptosis in the TME can contribute to the depletion of M2 macrophages (72) and facilitate the repolarization of M2 macrophages towards the M1 phenotype (68–70), which is associated with reduced tumour progression and metastasis (70,73). Crosstalk occurs between ferroptosis, the TME and macrophage polarization (Fig. 3). M1 macrophages can directly release peroxides, such as hydrogen peroxide (H2O2) (74), or they can release interferon gamma (IFNγ) and thereby downregulate the expression of glutamate-cystine antiporters via the JAK/STAT1 signalling pathway. Furthermore, M1 macrophages can activate ACSL4 to increase lipid peroxidation sensitivity (75), thereby facilitating ferroptosis in tumour cells (76). On the other hand, M2 macrophages participate in immune regulation through distinct mechanisms. They increase the expression of PD-L1 on tumour cells (77), and PD-L1 then binds to PD-1 on T cells, initiating programmed cell death in CTLs and thus increasing resistance to tumour ferroptosis (78). Additionally, M2 macrophages can activate the ERK signalling pathway by releasing IL-6, inhibiting the expression of system Xc- (79), which further modulates iron metabolism and immune responses in the TME. Similarly, NADPH oxidase 4 can be activated by TGF-β1 (80), which promotes the generation of ROS. In HeLa cells treated with IL-6 (81), the increase in phosphorylated ERK further corroborates this finding. Chen et al (82) reported that ACSL4 promotes the polarization of M2 macrophages towards the M1 phenotype, consequently reducing cell proliferation and invasion and inducing ferroptosis in nasopharyngeal carcinoma cells. Gu et al (68) utilized MIL88B nanoparticles containing RSL3 to activate ferroptosis in M2-polarized macrophages, resulting in a shift in cellular metabolic patterns and the repolarization of M2 cells towards the M1 phenotype. This process involves the inhibition of GPX4 expression and the promotion of lipid peroxidation. Notably, cancer cells may target ferroptosis in macrophages, thereby weakening their anticancer effects and causing immune resistance (83). Macrophage-associated exosomes in the TME inhibit ferroptosis in macrophages during lung metastasis, thereby promoting disease dissemination (73). Ferroptotic cell products can be divided into two categories of damage-associated molecular patterns (DAMPs), which bind to receptors on immune cells and transmit protective or aggressive signals to the adaptive immune system (84). ‘Eat me’ DAMPs such as High mobility group Box 1 (85) promote M1 polarization and assist immune clearance, whereas DAMPs such as Kirsten rat sarcoma 12D (86) promote M2 polarization and tumour progression. Therefore, the use of DAMPs to activate positive immune feedback can prevent tumour progression.
Ferroptosis and neutrophil trap network
NETs were discovered in 1996 (87). Unlike apoptosis and necrosis, NETs, an intricate meshwork of DNA strands and proteins that constitute a novel extracellular elimination mechanism by which neutrophils capture and destroy microorganisms, usually require the activation of neutrophils as well as the involvement of NADPH oxidases to produce ROS (88,89). NETs have primary tumorigenicity and promote angiogenesis, which mediates cancer proliferation, acts as an adhesion matrix to facilitate metastatic spread (90), and promotes endothelial-to-mesenchymal transition (91). Various cancer types, including breast (92), gastric (93) and colorectal cancer (94,95), are associated with NETs. Yang et al (96) reported that the coiled-coil domain containing 25 receptor on BCa cells can bind to NET DNA, serving as a chemoattractant and correlating with liver metastases. Therefore, NETs in patient serum may predict the incidence of early BCa liver metastases. Lee et al (97) reported similar findings in ovarian tumours, where inflammatory factors released by tumour cells stimulate neutrophils to become NET-like and capture circulating OC cells to promote tumour metastasis. The interaction between NETs and ferroptosis is closely related to metabolic reprogramming. Enhanced glycolysis is a characteristic of NET-induced proinflammatory and proangiogenic responses (98), which promote inflammation and ROS generation, whereas increased ROS and lipid peroxidation are characteristic of ferroptosis. It has been revealed that ferroptosis is one of the mechanisms of NET-induced sepsis-associated acute lung injury in alveolar epithelial cells (99). This process depends on methyltransferase-like 3-mediated HIF-1α m6A modification and subsequent mitochondrial metabolic reprogramming, accompanied by increased glycolysis and decreased oxidative phosphorylation. These metabolic changes promote the accumulation of ROS and the ferroptosis of alveolar epithelial cells. These findings provide a theoretical basis for the role of aerobic glycolysis in NET-induced ferroptosis. In addition, ferroptosis may partially explain the tumour-promoting characteristics of NETs. Necrotic tumour cells are initially immunogenic, but as the hypoxic and hypoglycaemic TME deteriorates, immune surveillance by immune cells decreases (100). Moreover, tumour-associated glycolysis increases, lactate and immunosuppressive metabolites accumulate, and necrotic cells gradually transform into immunosuppressive cells (101). NETs contribute to thrombosis and subsequent vascular occlusion (102), leading to hypoxia and nutrient deprivation in the TME, which further promotes immunosuppression and induces tumour cell resistance to ferroptosis. Merlin is considered a tumour suppressor. A recent study reported that NETs can inhibit Merlin phosphorylation through the TLR9/Merlin axis, leading to increased GPX4 expression, increasing the ferroptosis resistance of triple-negative BCa (TNBC) cells, and promoting the proliferation and invasion of TNBC cells (103). These findings indicate that blocking the key regulatory factors of NETs is beneficial for the treatment of TNBC.
Ferroptosis and mitochondrial autophagy
Mitochondrial autophagy refers to the selective removal of damaged or incomplete mitochondria through autophagy, which serves as a ‘scavenger’ for maintaining mitochondrial network homeostasis and functional integrity. Mitochondrial autophagy is a promising biomarker and potential therapeutic target (104) because its abnormal activity is associated with the growth and metastasis of cancers, particularly OC (105). In response to a certain level of oxidative stress, mitochondria can temporarily protect cells by promoting mitochondrial fusion (106), mitigating oxidative stress, inhibiting ferroptosis and maintaining their own stability (107). However, when damage exceeds the threshold for mitochondrial fusion, mitochondrial autophagy is activated (108), which helps maintain mitochondrial stability by reducing the accumulation of ROS, preserving iron homeostasis, activating cellular antioxidant systems, and enhancing cellular resistance to oxidative stress (109). Nevertheless, excessive activation of mitochondrial autophagy can have negative consequences. Sustained activation of mitochondrial autophagy can lead to the release of metal ions such as iron from mitochondria into the cytoplasm, providing an unstable iron source. Iron reacts with H2O2 in the subsequent Fenton reaction, generating large amounts of hydroxyl radicals (·OH), which are highly reactive oxidants that can initiate lipid peroxidation, damage cell membrane structures, impair functions, and promote ferroptosis (110). During tumour development, mitochondrial autophagy plays a dual role. On the one hand, it can eliminate dysfunctional mitochondria, alleviate oxidative stress, and prevent carcinogenesis (109). On the other hand, under adverse conditions (such as nutrient deprivation and hypoxia), mitochondrial autophagy can promote tumour cell survival and protect cells from apoptosis or necrosis. Therefore, mitochondrial autophagy is a crucial factor in controlling cancer cell quality.
Interaction between ferroptosis and cuproptosis
The concentration of copper is closely related to cellular activities such as cell proliferation and angiogenesis, as well as metabolic processes such as glycolysis and lipid transformation (111,112). Rapid cancer cell division and immune infiltration are inseparable from copper levels, and increased copper concentrations can be observed in various malignant tumours, including breast, gynaecological, lung, pancreatic, and gastric cancer (113–115). In 2022, Peter Tsvetkov first proposed the concept of ‘cuproptosis’, a type of regulated cell death that differs from apoptosis and follows ferroptosis. The process of cuproptosis involves the accumulation of copper-dependent fatty acid-acylated proteins and the reduction of Fe-S cluster proteins (116) (Fig. 4). Copper ions in the extracellular environment can be transported into cells by binding to copper ionophores such as elesclomol. The upstream regulator of protein acylation, FDX1/lipoyl synthase, is responsible for reducing Cu(II) to Cu(I) (117), which subsequently binds to lipoylated proteins within the tricarboxylic acid cycle (TCA) cycle in mitochondria, such as dihydrolipoamide S-acetyltransferase (118,119). During this process, lipoylated proteins accumulate, leading to increased ROS generation. Additionally, the stability of Fe-S clusters is disruptive, and the resulting protein toxicity stress serves as a trigger for cell death. This process can be reversed by copper chelators such as tetrathiomolybdate (120). Ferroptosis and cuproptosis involve similar regulatory processes, such as alterations in metal valence states, metabolism of macronutrients, and energy conversion, all of which affect cancer signalling pathways (121). There are also interactions between ferroptosis and cuproptosis. First, there are overlapping molecular components between these two modes of cell death. In a study investigating the pathogenesis of osteoarthritis, He et al (122) reported that 63 ferroptosis-related genes were closely related to 11 cuproptosis-related genes, and among these, they identified 40 novel characteristic genes associated primarily with inflammation, extracellular stimuli and autophagy. Luo et al (123) reported six ferroptosis genes (including TRIB3, PML and CD44) to be related to cuproptosis and were negatively correlated with survival rates. Second, copper can increase the ubiquitination and aggregation of GPX4, promoting its degradation and initiating ferroptosis. Copper chelators can specifically inhibit ferroptosis but have no effect on other forms of cell death, such as necrosis or apoptosis (124). Third, both forms of cell death can be triggered by the same stimuli, such as P53 activation and excessive ROS production (125,126). Finally, the progression of a single disease can involve both forms of cell death. In clear-cell renal cell carcinoma (ccRCC), the downregulation of FDX1, a key factor in cuproptosis, has been linked to tumorigenesis (123). The overexpression of Kruppel-like factor 2 downregulates GPX4 (127), increasing the sensitivity of ccRCC to ferroptosis and thereby hindering its growth and invasion (128).
Association of ferroptosis with gynaecological malignancies
Ferroptosis has dual effects on tumours. Resistance to ferroptosis is the nature of tumors. Inhibiting ferroptosis can promote cancer progression, whereas inducing ferroptosis has promising applications in tumour treatment. Ferroptosis can increase the sensitivity of tumour cells to traditional antitumour therapies such as chemotherapy and radiotherapy, providing a new strategy for targeting cancer cells that are difficult to eliminate with traditional treatments.
BCa. BCa is the most common malignant tumour in women, and non-surgical treatments for this disease include chemotherapy, human epidermal growth factor receptor 2-targeted therapy and endocrine therapy (129). Ferroptosis is involved in the drug resistance (130) and prognosis (131) of BCa. Zou et al (132) reported that VDAC3-derived crRNA binds to HSPB1 and inhibits its ubiquitination degradation, reducing the accumulation of ROS and LIP and thereby inhibiting ferroptosis in BCa cells with low levels of HER2, which in turn mediates trastuzumab deruxtecan resistance. Breast tissue has vigorous fatty acid metabolism, the expression of IL-6 and leptin is significantly increased in cancer-associated adipocytes, and these two substances are key factors in promoting tumour growth (133–135). Studies have shown that disrupting lipid metabolism reprogramming in BCa cells through ferroptosis can inhibit tumour activity and prevent tumour metastasis (136). Ferroptosis interferes with fatty acid metabolism by causing the oxidation of PUFAs to increase the production of PLOO−. This process damages the metabolism of cancer cells and thus promotes cancer cell death. Bobińskir et al (137) proposed that inducing ferroptosis causes an unbalanced fatty acid ratio in cancer cells, limiting the consumption and biosynthesis of BCa-related fatty acids and consequently leading to fatty acid deficiency and inhibiting tumour progression. In addition to interfering with fat metabolism, ferroptosis can reverse resistance to endocrine therapy in BCa. Tamoxifen (TAM) is a long-term endocrine drug for patients with oestrogen receptor (ER)+ BCa (138). Unfortunately, TAM cannot escape the development of chemoresistance (139). shown It has been reported that ferroptosis and the non-canonical NF-κB pathway activated by RelB are involved in BCa-TAM resistance: Activated RelB inhibits TAM-induced ferroptosis by upregulating GPX4, thereby promoting TAM resistance (140). By contrast, sustained inhibition of RelB transcriptional activation re-sensitizes TAM-resistant cells by increasing ferroptosis. The development of drugs related to RelB inhibitors is expected to promote the reversal of BCa resistance. The overexpression of DNAJC12, a member of the HSP family (HSP40), is a negative predictor of the response to neoadjuvant concurrent chemoradiotherapy (141). It has been revealed that overexpression of DNAJC12 inhibits ferroptosis and apoptosis through the HSP70-AKT signalling axis, thereby promoting BC resistance to chemotherapy and azithromycin. Studies have also shown that AKT or HSP70 inhibitors can reverse this process by repairing broken caspase3 and reducing GPX4 and SLC7A11 levels, providing new treatments for BCa chemotherapy resistance (142). TNBC, characterized by the absence of ER, progesterone receptor (PR) and HER2 (143), is the subtype of BCa that is the most difficult to treat (144). TNBC is rich in iron and lipids, making the induction of ferroptosis a viable therapeutic strategy (31,145). Yu et al (146) reported that TFRC is highly expressed in ER+ tissues and that reduced ER expression can increase TFRC expression, suggesting that ER plays a regulatory role in TFRC expression. Timmerman et al (147) reported that TNBC cells rely on glutamine and that reducing intracellular glutamine or inhibiting system Xc-can increase ROS in TNBC, inhibiting tumour progression.
Cervical cancer
The incidence rate of cervical cancer among young women has been increasing, which is a cause of serious concern. The annual mortality rate of cervical cancer exceeds 300,000, making it one of the cancers with the highest mortality rate among women worldwide, along with BCa, colorectal and lung cancer (3). Research has revealed the involvement of ferroptosis in the transformation of normal cervical cells into squamous intraepithelial lesion (SIL), the progression of SIL, and its transformation into cervical squamous cell carcinoma (148). Cervical cancer cells can inhibit ferroptosis through circular RNAs (149,150), hypoxia (151) and the proliferation of M1 macrophages (152), enabling them to survive and proliferate under ferroptotic stress (153). Inducing ferroptosis by targeting the characteristics of cervical cancer that resist ferroptosis provides a new prospective therapeutic approach. Oleanolic acid (OA) is a natural anticancer agent (154). It has been identified that OA targets and promotes ACSL4-mediated ferroptosis, which promotes the biosynthesis of PUFA-PLs and increases lipid peroxidation, thereby inhibiting the proliferation of cervical cancer cells (155). Dihydroartemisinin (DHA) is the main active metabolite of artemisinin and its derivatives and has a variety of low-toxicity anticancer properties. DHA can induce NCOA4-mediated ferritin autophagy, thereby leading to an increase in the intracellular LIP, aggravating the Fenton reaction to produce excessive ROS, and consequently enhancing ferroptosis in cervical cancer. The combination of DHA and doxorubicin has a highly synergistic elimination effect on cervical cancer cells, which is also related to ferroptosis (156). In addition to chemotherapy, ferroptosis induction combined with radiotherapy has unexpected effects. Radiotherapy can not only activate NRF2-mediated GPX4 transcription but also inhibit lysosome-mediated GPX4 degradation, thereby inducing cancer cell tolerance to ferroptosis and radioresistance. Tubastatin A, a histone deacetylase 6 inhibitor, significantly promotes radiotherapy-induced lipid peroxidation and tumour suppression by inhibiting GPX4 enzyme activity, overcoming the ferroptosis resistance and radioresistance of cancer cells (157). Various ferroptosis inducers, such as sorafenib and sulfaquinoxaline, can act as radiosensitizers by inhibiting the activity of SLC7A11 and GPX4. Combining radiotherapy with ferroptosis inducers is expected to overcome radiotherapy resistance in patients with cervical cancer (158).
OC
In total, ~70% of patients are already in the advanced stage at the time of their first diagnosis of OC (159). Multiple mechanisms, including glycolysis, fatty acid synthesis and angiogenesis mimicry, collectively contribute to the development of OC (160–162). Platinum drugs combined with paclitaxel are the traditional first-line treatment options for OC, but chemotherapy resistance and high recurrence rates often occur during treatment (163,164). Studies have shown that both cisplatin and paclitaxel can act on the GPX4-GSH axis. The former forms a complex with glutathione (165), and the latter downregulates the expression of system Xc-. Both can reduce GSH levels, increase oxidative stress and lipid peroxidation, and effectively induce ferroptosis (166). The characteristics of platinum-resistant cancer cells may confer therapeutic benefits. Wang et al (167) reported that overexpression of the Wnt receptor frzzled-7 (FZD7) activates the oncogenic factor TP63, upregulates the glutathione metabolic pathway, increases GPX expression, and protects cancer cells from chemotherapy-induced peroxidative damage. After treatment with GPX4 inhibitors, FZD7+ platinum-resistant OC cells become more sensitive to platinum drugs, filling the therapeutic gap in treating platinum-resistant cancers (168). Curcumin sensitizes cisplatin-resistant OC cells to cisplatin-induced apoptosis. However, its low bioavailability limits its application. The development of the curcumin derivative NLO1 has greatly improved the antitumour effects of curcumin. Ferroptosis is involved in this process (169). NLO1 can downregulate HCAR1/MCT1 expression, activate the AMPK-SREBP1 pathway, downregulate GPX4 expression, induce ferroptosis in the Anglne and HO8910PM OC cell lines, and inhibit OC proliferation. Erastin induces lipid ROS production and mitochondrial dysfunction, consumes GSH, weakens the antioxidant capacity of cells, and triggers ferroptosis. It has a synergistic effect with cisplatin in inducing ferroptosis to inhibit the growth of OC cells in vitro and in vivo, thereby increasing the cytotoxic effect of cisplatin while reducing side effects (170). In addition, it has been revealed that combined treatment with cisplatin and natural antitumour compounds isolated from the roots of Lithospermum officinale can increase the levels of the ferroptosis-related molecular markers ROS, LPO and Fe2+, downregulate GPX4, induce ferroptosis, and synergistically reduce the viability of cisplatin-resistant OC cells (171). PARP is an important target for cancer treatment and is involved in DNA repair, methylation, transcriptional regulation and transcriptional metabolism (172,173). The pharmacological inhibition or genetic deletion of PARP promotes ferroptosis by inhibiting SLC7A11-mediated GSH biosynthesis in a p53-dependent manner. Olaparib is the most classic and effective PARP inhibitor (174,175). It is used in combination with a ferroptosis inducer (FIN) to sensitize BRCA-mutated OC cells to PARP inhibitors (176). Arsenic trioxide is used in combination with olaparib to activate the AMPKα pathway, inhibit SCD1 expression, promote lipid peroxidation, and ultimately induce ferroptosis, increasing the effect of olaparib on platinum-resistant OC (177). Targeted therapy against ferroptosis is expected to open new avenues for the treatment of platinum-resistant OC.
Carcinoma of the endometrium
Endometrial cancer (EC) is a type of cancer that arises from the malignant transformation of endometrial epithelial cells (178). Metabolic reprogramming is involved in the development of EC. Studies have shown that EC is dependent on glucose and glutamine and overexpresses SLC7A11 (179,180), which not only affects cellular antioxidant defence (181) but also influences the induction of ferroptosis in tumour cells. EC cells rely on glycolysis-lipogenesis metabolism (182). A high glycolytic rate inhibits the TCA cycle, reducing the production of NADH and ROS. Conversely, inhibiting glycolysis in ECs promotes the TCA cycle and oxidative phosphorylation, thereby inducing ferroptosis and inhibiting tumour progression (183). Glucose oxidase nanoparticles have been utilized to target tumour cells (184), where they catalyse glucose decomposition and increase H2O2 concentrations, thereby reducing glucose levels and increasing ROS in tumours (185). The glutamine dependency of EC can be exploited by upregulating the glutamine transporter ASCT2 in ECs, which in turn reduces intracellular glutamine levels and inhibits EC cell proliferation (179). Given that SLC7A11 is a critical player in ferroptosis, therapies targeting SLC7A11 can also be applied to EC. The use of ferroptosis inducers (such as sulfasalazine, erastin and RSL3) to treat megestrol acetate (MPA)-resistant EC downregulates SLC7A11 and GPX4, significantly reducing the survival rate of MPA-resistant EC-1 cells (185). In addition, juglone (186) activates ferroptosis in EC cells by upregulating heme oxygenase 1, resulting in the release of free iron from haem in ECs, the production of lipid peroxides, and the reduction of MDA. These results suggest a new therapeutic approach for the treatment of EC.
Conclusions and future perspectives
The mechanism of ferroptosis involves iron homeostasis, lipid metabolism and antioxidant systems. Ferroptosis is a programmed cell death process that can be regulated by drugs or genetic means, either inducers or inhibitors. In the TME, tumour cells resist ferroptosis by activating hypoxia-related induction factors to reduce intracellular iron storage or by increasing antioxidant signals (187). In the tumour immune microenvironment, inducing M2 macrophage polarization is beneficial for tumour survival and progression. Ferroptotic cells can release DAMPs to activate the immune system, induce macrophage polarization, and initiate signals related to protection or resistance to ferroptosis. The depletion of M2 tumour-associated macrophages in the TME and M1 repolarization can activate ferroptosis and prevent tumour progression and metastasis (70,72). The polarization state and function of macrophages in the TME are significantly influenced by iron metabolism. Future research needs to further explore the specific mechanisms of iron metabolism in macrophage polarization and tumour immunotherapy and discover how to balance the anticancer and cancer-promoting effects of ferroptosis in macrophages and direct iron regulation in macrophages towards the inhibition of cancer progression to develop more effective therapeutic strategies. Inflammatory factors secreted by tumours can induce the formation of NETs, which protect tumour cells from cytotoxic immunity and impair tumour clearance (188). In BCa (92), they can act as chemokines to mediate the distant metastasis of tumours and can also promote tumour progression by mediating ferroptosis resistance (103). Interestingly, in non-tumour cells, such as alveolar epithelial cells (189) and intestinal endothelial cells (190), NETs can cause disease phenotypes by inducing ferroptosis. The mechanism by which NETs resist ferroptosis in tumour tissues but induce ferroptosis in non-tumour tissues has not yet been elucidated. Abnormalities in mitochondrial structure and function lead to abnormal levels and distributions of metal ions (191). Mitochondrial autophagy contributes to mitochondrial quality control. The resulting autophagic mitochondria cannot only isolate abnormal mitochondria but also serve as new iron storage space to prevent the generation of ROS by the Fenton reaction from inducing further cell death (110). However, excessive mitochondrial autophagy is a sufficient source of iron for ferroptosis. Cuproptosis is another form of metal ion-dependent cell death that was discovered after ferroptosis and is closely related to multiple signalling pathways and tumour-related biological behaviours (192). The ferroptosis inducers sorafenib and erastin can increase cuproptosis in primary liver cancer, upregulate protein fatty acylation by blocking mitochondrial matrix-associated protease-mediated degradation of the FDX1 protein, and reduce the synthesis of the intracellular copper chelator GSH by inhibiting cystine import (193). Cuproptosis and ferroptosis can be induced by the same stimuli and share interacting molecules and genes, and cuproptosis can promote ferroptosis (194). These findings indicate that ferroptosis is not an independent pathway involved in disease. Ferroptosis combines mechanisms involved in tumour occurrence and development, such as cellular immunity-macrophage polarization, organelle defence-mitochondrial autophagy, the cell clearance-neutrophil capture network, and the interactions of other metal ions with copper. Among these mechanisms, whether ferroptosis is the main trunk or a side branch, has great application prospects in oncology research. Examples of inducers and inhibitors of ferroptosis are included in Table I.
At present, the drug resistance of gynaecological tumours is a worldwide problem that urgently needs to be solved. Ferroptosis has been found to be involved in tumorigenesis, the destruction of the immune microenvironment, tumour proliferation and metastasis, and the treatment of malignant gynaecological tumours. The current therapeutic strategies for inducing ferroptosis in tumour cells include targeting anti-iron oxidation pathways and ferroptosis metabolic pathways. The former weakens the antioxidant capacity of cancer cells mainly by inhibiting the GSH-GPX4 axis and inducing tumour cell death. The latter induces ferroptosis in cancer cells by regulating ferroptosis metabolic systems such as iron metabolism and lipid metabolism. Research on related drugs in female patients is also in full swing. Ferroptosis can supplement the therapeutic mechanisms of existing drugs, such as curcumin derivatives, or it can be combined with existing drugs, such as tamoxifen combined with RELB inhibitors, erastin combined with platinum, and FIN combined with olaparib, to promote the antitumour effect, reverse chemotherapy resistance or reduce adverse drug reactions. In addition, ferroptosis combined with radiotherapy is expected to reverse the radiotherapy resistance of tumour cells. Ferroptosis has the potential to overcome difficulties in the traditional treatment of gynaecological malignancies, inhibit tumour cell proliferation and metastasis, and resolve tumour resistance. However, the existing research on ferroptosis remains experimental, and further research is needed to enable clinical translation.
Acknowledgements
Not applicable.
Funding
The present study was supported by the Natural Science Foundation of China (82303246), the Natural Science Foundation of Hunan Province (2023JJ41066), Health Research Project of Hunan Health Commission in 2024 (W20243173) and the Project of Hunan Provincial Health Commission (202205034020).
Availability of data and materials
Not applicable.
Authors' contributions
PTW and YKL structured the ideas for the document and drafted the outline. PTW, JLC and HL were responsible for the writing of the original manuscript and the creation of figures and table. HYL and JZ reviewed and revised the manuscript. All authors read and approved the final version of the manuscript. Data authentication is not applicable.
Ethics approval and consent to participate
Not applicable.
Patient consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
References
Torre LA, Islami F, Siegel RL, Ward EM and Jemal A: Global cancer in women: Burden and trends. Cancer Epidemiol Biomarkers Prev. 26:444–457. 2017. View Article : Google Scholar : PubMed/NCBI | |
Abu Samaan TM, Samec M, Liskova A, Kubatka P and Büsselberg D: Paclitaxel's mechanistic and clinical effects on breast cancer. Biomolecules. 9:7892019. View Article : Google Scholar : PubMed/NCBI | |
Vu M, Yu J, Awolude OA and Chuang L: Cervical cancer worldwide. Curr Probl Cancer. 42:457–465. 2018. View Article : Google Scholar : PubMed/NCBI | |
Ledermann JA: Front-line therapy of advanced ovarian cancer: New approaches. Ann Oncol. 28 (Suppl_8):viii46–viii50. 2017. View Article : Google Scholar : PubMed/NCBI | |
Fillon M: Opportunistic salpingectomy may reduce ovarian cancer risk. CA Cancer J Clin. 72:97–99. 2022. View Article : Google Scholar : PubMed/NCBI | |
Torre LA, Trabert B, DeSantis CE, Miller KD, Samimi G, Runowicz CD, Gaudet MM, Jemal A and Siegel RL: Ovarian cancer statistics, 2018. CA Cancer J Clin. 68:284–296. 2018. View Article : Google Scholar : PubMed/NCBI | |
Mirza MR, Coleman RL, González-Martín A, Moore KN, Colombo N, Ray-Coquard I and Pignata S: The forefront of ovarian cancer therapy: Update on PARP inhibitors. Ann Oncol. 31:1148–1159. 2020. View Article : Google Scholar : PubMed/NCBI | |
Kalampokas E, Giannis G, Kalampokas T, Papathanasiou AA, Mitsopoulou D, Tsironi E, Triantafyllidou O, Gurumurthy M, Parkin DE, Cairns M and Vlahos NF: Current approaches to the management of patients with endometrial cancer. Cancers (Basel). 14:45002022. View Article : Google Scholar : PubMed/NCBI | |
Brooks RA, Fleming GF, Lastra RR, Lee NK, Moroney JW, Son CH, Tatebe K and Veneris JL: Current recommendations and recent progress in endometrial cancer. CA Cancer J Clin. 69:258–279. 2019. View Article : Google Scholar : PubMed/NCBI | |
Dolma S, Lessnick SL, Hahn WC and Stockwell BR: Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells. Cancer Cell. 3:285–296. 2003. View Article : Google Scholar : PubMed/NCBI | |
Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, et al: Ferroptosis: An iron-dependent form of nonapoptotic cell death. Cell. 149:1060–1072. 2012. View Article : Google Scholar : PubMed/NCBI | |
Conrad M and Pratt DA: The chemical basis of ferroptosis. Nat Chem Biol. 15:1137–1147. 2019. View Article : Google Scholar : PubMed/NCBI | |
Yi J, Zhu J, Wu J, Thompson CB and Jiang X: Oncogenic activation of PI3K-AKT-mTOR signaling suppresses ferroptosis via SREBP-mediated lipogenesis. Proc Natl Acad Sci USA. 117:31189–31197. 2020. View Article : Google Scholar : PubMed/NCBI | |
Friedmann Angeli JP, Krysko DV and Conrad M: Ferroptosis at the crossroads of cancer-acquired drug resistance and immune evasion. Nat Rev Cancer. 19:405–414. 2019. View Article : Google Scholar : PubMed/NCBI | |
Lei G, Zhuang L and Gan B: Targeting ferroptosis as a vulnerability in cancer. Nat Rev Cancer. 22:381–396. 2022. View Article : Google Scholar : PubMed/NCBI | |
Mao X, Liu K, Shen S, Meng L and Chen S: Ferroptosis, a new form of cell death: Mechanisms, biology and role in gynecological malignant tumor. Am J Cancer Res. 13:2751–2762. 2023.PubMed/NCBI | |
Chen Z, Han F, Du Y, Shi H and Zhou W: Hypoxic microenvironment in cancer: Molecular mechanisms and therapeutic interventions. Signal Transduct Target Ther. 8:702023. View Article : Google Scholar : PubMed/NCBI | |
Wu Q, You L, Nepovimova E, Heger Z, Wu W, Kuca K and Adam V: Hypoxia-inducible factors: Master regulators of hypoxic tumor immune escape. J Hematol Oncol. 15:772022. View Article : Google Scholar : PubMed/NCBI | |
Semenza GL: Pharmacologic targeting of Hypoxia-inducible factors. Annu Rev Pharmacol Toxicol. 59:379–403. 2019. View Article : Google Scholar : PubMed/NCBI | |
Fuhrmann DC, Mondorf A, Beifuß J, Jung M and Brüne B: Hypoxia inhibits ferritinophagy, increases mitochondrial ferritin, and protects from ferroptosis. Redox Biol. 36:1016702020. View Article : Google Scholar : PubMed/NCBI | |
Fuhrmann DC and Brüne B: A graphical journey through iron metabolism, microRNAs, and hypoxia in ferroptosis. Redox Biol. 54:1023652022. View Article : Google Scholar : PubMed/NCBI | |
Feng X, Wang S, Sun Z, Dong H, Yu H, Huang M and Gao X: Ferroptosis enhanced diabetic renal tubular injury via HIF-1α/HO-1 pathway in db/db mice. Front Endocrinol (Lausanne). 12:6263902021. View Article : Google Scholar : PubMed/NCBI | |
Yuan S, Wei C, Liu G, Zhang L, Li J, Li L, Cai S and Fang L: Sorafenib attenuates liver fibrosis by triggering hepatic stellate cell ferroptosis via HIF-1α/SLC7A11 pathway. Cell Prolif. 55:e131582022. View Article : Google Scholar : PubMed/NCBI | |
Liu XJ, Lv YF, Cui WZ, Li Y, Liu Y, Xue YT and Dong F: Icariin inhibits hypoxia/reoxygenation-induced ferroptosis of cardiomyocytes via regulation of the Nrf2/HO-1 signaling pathway. FEBS Open Bio. 11:2966–2976. 2021. View Article : Google Scholar : PubMed/NCBI | |
Adrover JM, McDowell SAC, He XY, Quail DF and Egeblad M: NETworking with cancer: The bidirectional interplay between cancer and neutrophil extracellular traps. Cancer Cell. 41:505–526. 2023. View Article : Google Scholar : PubMed/NCBI | |
Ge W and Wu W: Influencing Factors and significance of Tumor-associated Macrophage polarization in tumor microenvironment. Zhongguo Fei Ai Za Zhi. 26:228–237. 2023.(In Chinese). PubMed/NCBI | |
Hernansanz-Agustín P, Choya-Foces C, Carregal-Romero S, Ramos E, Oliva T, Villa-Piña T, Moreno L, Izquierdo-Álvarez A, Cabrera-García JD, Cortés A, et al: Na+ controls hypoxic signalling by the mitochondrial respiratory chain. Nature. 586:287–291. 2020. View Article : Google Scholar : PubMed/NCBI | |
Jung J, Zhang Y, Celiku O, Zhang W, Song H, Williams BJ, Giles AJ, Rich JN, Abounader R, Gilbert MR and Park DM: Mitochondrial NIX promotes tumor survival in the hypoxic niche of glioblastoma. Cancer Res. 79:5218–5232, 20193. View Article : Google Scholar : PubMed/NCBI | |
Kuo CL, Ponneri Babuharisankar A, Lin YC, Lien HW, Lo YK, Chou HY, Tangeda V, Cheng LC, Cheng AN and Lee AY: Mitochondrial oxidative stress in the tumor microenvironment and cancer immunoescape: Foe or friend? J Biomed Sci. 29:742022. View Article : Google Scholar : PubMed/NCBI | |
Xiao C, Wang X, Li S, Zhang Z, Li J, Deng Q, Chen X, Yang X and Li Z: A cuproptosis-based nanomedicine suppresses triple negative breast cancers by regulating tumor microenvironment and eliminating cancer stem cells. Biomaterials. 313:1227632025. View Article : Google Scholar : PubMed/NCBI | |
Doll S, Proneth B, Tyurina YY, Panzilius E, Kobayashi S, Ingold I, Irmler M, Beckers J, Aichler M, Walch A, et al: ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition. Nat Chem Biol. 13:91–98. 2017. View Article : Google Scholar : PubMed/NCBI | |
Dixon SJ, Winter GE, Musavi LS, Lee ED, Snijder B, Rebsamen M, Superti-Furga G and Stockwell BR: Human haploid cell genetics reveals roles for lipid metabolism genes in nonapoptotic cell death. ACS Chem Biol. 10:1604–1609. 2015. View Article : Google Scholar : PubMed/NCBI | |
Yuan H, Li X, Zhang X, Kang R and Tang D: Identification of ACSL4 as a biomarker and contributor of ferroptosis. Biochem Biophys Res Commun. 478:1338–1343. 2016. View Article : Google Scholar : PubMed/NCBI | |
Zou Y, Li H, Graham ET, Deik AA, Eaton JK, Wang W, Sandoval-Gomez G, Clish CB, Doench JG and Schreiber SL: Cytochrome P450 oxidoreductase contributes to phospholipid peroxidation in ferroptosis. Nat Chem Biol. 16:302–309. 2020. View Article : Google Scholar : PubMed/NCBI | |
Koleini N, Shapiro JS, Geier J and Ardehali H: Ironing out mechanisms of iron homeostasis and disorders of iron deficiency. J Clin Invest. 131:e1486712021. View Article : Google Scholar : PubMed/NCBI | |
Luck AN and Mason AB: Transferrin-mediated cellular iron delivery. Curr Top Membr. 69:3–35. 2012. View Article : Google Scholar : PubMed/NCBI | |
Mancias JD, Wang X, Gygi SP, Harper JW and Kimmelman AC: Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy. Nature. 509:105–109. 2014. View Article : Google Scholar : PubMed/NCBI | |
Yambire KF, Rostosky C, Watanabe T, Pacheu-Grau D, Torres-Odio S, Sanchez-Guerrero A, Senderovich O, Meyron-Holtz EG, Milosevic I, Frahm J, et al: Impaired lysosomal acidification triggers iron deficiency and inflammation in vivo. Elife. 8:e510312019. View Article : Google Scholar : PubMed/NCBI | |
Zhang DD: Ironing out the details of ferroptosis. Nat Cell Biol. 26:1386–1393. 2024. View Article : Google Scholar : PubMed/NCBI | |
Chen X, Yu C, Kang R, Kroemer G and Tang D: Cellular degradation systems in ferroptosis. Cell Death Differ. 28:1135–1148. 2021. View Article : Google Scholar : PubMed/NCBI | |
Liu J, Kang R and Tang D: Signaling pathways and defense mechanisms of ferroptosis. FEBS J. 289:7038–7050. 2022. View Article : Google Scholar : PubMed/NCBI | |
Bersuker K, Hendricks JM, Li Z, Magtanong L, Ford B, Tang PH, Roberts MA, Tong B, Maimone TJ and Zoncu R: The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. Nature. 575:688–692. 2019. View Article : Google Scholar : PubMed/NCBI | |
Doll S, Freitas FP, Shah R, Aldrovandi M, da Silva MC, Ingold I, Goya Grocin A, Xavier da Silva TN, Panzilius E, Scheel CH, et al: FSP1 is a glutathione-independent ferroptosis suppressor. Nature. 575:693–698. 2019. View Article : Google Scholar : PubMed/NCBI | |
Garcia-Bermudez J and Birsoy K: A mitochondrial gatekeeper that helps cells escape death by ferroptosis. Nature. 593:514–515. 2021. View Article : Google Scholar : PubMed/NCBI | |
Mao C, Liu X, Zhang Y, Lei G, Yan Y, Lee H, Koppula P, Wu S, Zhuang L, Fang B, et al: DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer. Nature. 593:586–590. 2021. View Article : Google Scholar : PubMed/NCBI | |
Zhao L, Zhou X, Xie F and Zhang L, Yan H, Huang J, Zhang C, Zhou F, Chen J and Zhang L: Ferroptosis in cancer and cancer immunotherapy. Cancer Commun (Lond). 42:88–116. 2022. View Article : Google Scholar : PubMed/NCBI | |
Kraft VAN, Bezjian CT, Pfeiffer S, Ringelstetter L, Müller C, Zandkarimi F, Merl-Pham J, Bao X, Anastasov N, Kössl J, et al: GTP Cyclohydrolase 1/Tetrahydrobiopterin Counteract Ferroptosis through lipid remodeling. ACS Cent Sci. 6:41–53. 2020. View Article : Google Scholar : PubMed/NCBI | |
Yagoda N, von Rechenberg M, Zaganjor E, Bauer AJ, Yang WS, Fridman DJ, Wolpaw AJ, Smukste I, Peltier JM, Boniface JJ, et al: RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels. Nature. 447:864–868. 2007. View Article : Google Scholar : PubMed/NCBI | |
Yang WS and Stockwell BR: Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells. Chem Biol. 15:234–245. 2008. View Article : Google Scholar : PubMed/NCBI | |
Tomaskova Z, Gaburjakova J, Brezova A and Gaburjakova M: Inhibition of anion channels derived from mitochondrial membranes of the rat heart by stilbene disulfonate-DIDS. J Bioenerg Biomembr. 39:301–311. 2007. View Article : Google Scholar : PubMed/NCBI | |
Xue X, Ramakrishnan SK, Weisz K, Triner D, Xie L, Attili D, Pant A, Győrffy B, Zhan M, Carter-Su C, et al: Iron uptake via DMT1 integrates cell cycle with JAK-STAT3 signaling to promote colorectal tumorigenesis. Cell Metab. 24:447–461. 2016. View Article : Google Scholar : PubMed/NCBI | |
Song Q, Peng S, Sun Z, Heng X and Zhu X: Temozolomide drives ferroptosis via a DMT1-Dependent pathway in glioblastoma cells. Yonsei Med J. 62:843–849. 2021. View Article : Google Scholar : PubMed/NCBI | |
Li J, Lama R, Galster SL, Inigo JR, Wu J, Chandra D, Chemler SR and Wang X: Small-Molecule MMRi62 induces ferroptosis and inhibits metastasis in pancreatic cancer via degradation of ferritin heavy chain and mutant p53. Mol Cancer Ther. 21:535–545. 2022. View Article : Google Scholar : PubMed/NCBI | |
Feng J, Lu PZ, Zhu GZ, Hooi SC, Wu Y, Huang XW, Dai HQ, Chen PH, Li ZJ, Su WJ, et al: ACSL4 is a predictive biomarker of sorafenib sensitivity in hepatocellular carcinoma. Acta Pharmacol Sin. 42:160–170. 2021. View Article : Google Scholar : PubMed/NCBI | |
Wenz C, Faust D, Linz B, Turmann C, Nikolova T, Bertin J, Gough P, Wipf P, Schröder AS, Krautwald S and Dietrich C: t-BuOOH induces ferroptosis in human and murine cell lines. Arch Toxicol. 92:759–775. 2018. View Article : Google Scholar : PubMed/NCBI | |
Yang WS, SriRamaratnam R, Welsch ME, Shimada K, Skouta R, Viswanathan VS, Cheah JH, Clemons PA, Shamji AF and Clish CB: Regulation of ferroptotic cancer cell death by GPX4. Cell. 156:317–331. 2014. View Article : Google Scholar : PubMed/NCBI | |
Li J, Cao F, Yin HL, Huang ZJ, Lin ZT, Mao N, Sun B and Wang G: Ferroptosis: Past, present and future. Cell Death Dis. 11:882020. View Article : Google Scholar : PubMed/NCBI | |
Wu Z, Geng Y, Lu X, Shi Y, Wu G, Zhang M, Shan B, Pan H and Yuan J: Chaperone-mediated autophagy is involved in the execution of ferroptosis. Proc Natl Acad Sci USA. 116:2996–3005. 2019. View Article : Google Scholar : PubMed/NCBI | |
Yoshioka H, Kawamura T, Muroi M, Kondoh Y, Honda K, Kawatani M, Aono H, Waldmann H, Watanabe N and Osada H: Identification of a small molecule that enhances ferroptosis via inhibition of ferroptosis suppressor protein 1 (FSP1). ACS Chem Biol. 17:483–491. 2022. View Article : Google Scholar : PubMed/NCBI | |
Zhao Y, Yin W, Yang Z, Sun J, Chang J, Huang L, Xue L, Zhang X, Zhi H, Chen S, et al: Nanotechnology-enabled M2 macrophage polarization and ferroptosis inhibition for targeted inflammatory bowel disease treatment. J Control Release. 367:339–353. 2024. View Article : Google Scholar : PubMed/NCBI | |
Zhang H, Deng T, Liu R, Ning T, Yang H, Liu D, Zhang Q, Lin D, Ge S, Bai M, et al: CAF secreted miR-522 suppresses ferroptosis and promotes acquired chemo-resistance in gastric cancer. Mol Cancer. 19:432020. View Article : Google Scholar : PubMed/NCBI | |
Ishii T, Bannai S and Sugita Y: Mechanism of growth stimulation of L1210 cells by 2-mercaptoethanol in vitro. Role of the mixed disulfide of 2-mercaptoethanol and cysteine. J Biol Chem. 256:12387–12392. 1981. View Article : Google Scholar : PubMed/NCBI | |
Gordon S: Alternative activation of macrophages. Nat Rev Immunol. 3:23–35. 2003. View Article : Google Scholar : PubMed/NCBI | |
Murdoch C, Giannoudis A and Lewis CE: Mechanisms regulating the recruitment of macrophages into hypoxic areas of tumors and other ischemic tissues. Blood. 104:2224–2234. 2004. View Article : Google Scholar : PubMed/NCBI | |
Boutilier AJ and Elsawa SF: Macrophage polarization states in the tumor microenvironment. Int J Mol Sci. 22:69952021. View Article : Google Scholar : PubMed/NCBI | |
Yin M, Li X, Tan S, Zhou HJ, Ji W, Bellone S, Xu X, Zhang H, Santin AD, Lou G and Min W: Tumor-associated macrophages drive spheroid formation during early transcoelomic metastasis of ovarian cancer. J Clin Invest. 126:4157–4173. 2016. View Article : Google Scholar : PubMed/NCBI | |
Recalcati S, Locati M, Gammella E, Invernizzi P and Cairo G: Iron levels in polarized macrophages: Regulation of immunity and autoimmunity. Autoimmun Rev. 11:883–889. 2012. View Article : Google Scholar : PubMed/NCBI | |
Gu Z, Liu T, Liu C, Yang Y, Tang J, Song H, Wang Y, Yang Y and Yu C: Ferroptosis-strengthened metabolic and inflammatory regulation of Tumor-associated macrophages provokes potent tumoricidal activities. Nano Lett. 21:6471–6479. 2021. View Article : Google Scholar : PubMed/NCBI | |
Hao X, Zheng Z, Liu H, Zhang Y, Kang J, Kong X, Rong D, Sun G, Sun G, Liu L, et al: Inhibition of APOC1 promotes the transformation of M2 into M1 macrophages via the ferroptosis pathway and enhances anti-PD1 immunotherapy in hepatocellular carcinoma based on single-cell RNA sequencing. Redox Biol. 56:1024632022. View Article : Google Scholar : PubMed/NCBI | |
Li LG, Peng XC, Yu TT, Xu HZ, Han N, Yang XX, Li QR, Hu J, Liu B, Yang ZY, et al: Dihydroartemisinin remodels macrophage into an M1 phenotype via ferroptosis-mediated DNA damage. Front Pharmacol. 13:9498352022. View Article : Google Scholar : PubMed/NCBI | |
Recalcati S, Locati M, Marini A, Santambrogio P, Zaninotto F, De Pizzol M, Zammataro L, Girelli D and Cairo G: Differential regulation of iron homeostasis during human macrophage polarized activation. Eur J Immunol. 40:824–835. 2010. View Article : Google Scholar : PubMed/NCBI | |
Zhao YY, Lian JX, Lan Z, Zou KL, Wang WM and Yu GT: Ferroptosis promotes anti-tumor immune response by inducing immunogenic exposure in HNSCC. Oral Dis. 29:933–941. 2023. View Article : Google Scholar : PubMed/NCBI | |
Chen W, Zuo F, Zhang K, Xia T, Lei W, Zhang Z, Bao L and You Y: Exosomal MIF derived from nasopharyngeal carcinoma promotes metastasis by repressing ferroptosis of macrophages. Front Cell Dev Biol. 9:7911872021. View Article : Google Scholar : PubMed/NCBI | |
Jakubczyk K, Dec K, Kałduńska J, Kawczuga D, Kochman J and Janda K: Reactive oxygen species-sources, functions, oxidative damage. Pol Merkur Lekarski. 48:124–127. 2020.PubMed/NCBI | |
Wang W, Green M, Choi JE, Gijón M, Kennedy PD, Johnson JK, Liao P, Lang X, Kryczek I, Sell A, et al: CD8+ T cells regulate tumour ferroptosis during cancer immunotherapy. Nature. 569:270–274. 2019. View Article : Google Scholar : PubMed/NCBI | |
Haschka D, Hoffmann A and Weiss G: Iron in immune cell function and host defense. Semin Cell Dev Biol. 115:27–36. 2021. View Article : Google Scholar : PubMed/NCBI | |
Wen ZF, Liu H, Gao R, Zhou M, Ma J, Zhang Y, Zhao J, Chen Y, Zhang T, Huang F, et al: Tumor cell-released autophagosomes (TRAPs) promote immunosuppression through induction of M2-like macrophages with increased expression of PD-L1. J Immunother Cancer. 6:1512018. View Article : Google Scholar : PubMed/NCBI | |
Farhood B, Najafi M and Mortezaee K: CD8+ cytotoxic T lymphocytes in cancer immunotherapy: A review. J Cell Physiol. 234:8509–8521. 2019. View Article : Google Scholar : PubMed/NCBI | |
Yang L, Guo J, Yu N, Liu Y, Song H, Niu J and Gu Y: Tocilizumab mimotope alleviates kidney injury and fibrosis by inhibiting IL-6 signaling and ferroptosis in UUO model. Life Sci. 261:1184872020. View Article : Google Scholar : PubMed/NCBI | |
Carmona-Cuenca I, Roncero C, Sancho P, Caja L, Fausto N, Fernández M and Fabregat I: Upregulation of the NADPH oxidase NOX4 by TGF-beta in hepatocytes is required for its pro-apoptotic activity. J Hepatol. 49:965–976. 2008. View Article : Google Scholar : PubMed/NCBI | |
Yang L, Xing R, Li C, Liu Y, Sun L, Liu X and Wang Y: Active immunization with Tocilizumab mimotopes induces specific immune responses. BMC Biotechnol. 15:462015. View Article : Google Scholar : PubMed/NCBI | |
Chen P, Wang D, Xiao T, Gu W, Yang H, Yang M and Wang H: ACSL4 promotes ferroptosis and M1 macrophage polarization to regulate the tumorigenesis of nasopharyngeal carcinoma. Int Immunopharmacol. 122:1106292023. View Article : Google Scholar : PubMed/NCBI | |
Puylaert P, Roth L, Van Praet M, Pintelon I, Dumitrascu C, van Nuijs A, Klejborowska G, Guns PJ, Berghe TV, Augustyns K, et al: Effect of erythrophagocytosis-induced ferroptosis during angiogenesis in atherosclerotic plaques. Angiogenesis. 26:505–522. 2023. View Article : Google Scholar : PubMed/NCBI | |
Tang R, Xu J, Zhang B, Liu J, Liang C, Hua J, Meng Q, Yu X and Shi S: Ferroptosis, necroptosis, and pyroptosis in anticancer immunity. J Hematol Oncol. 13:1102020. View Article : Google Scholar : PubMed/NCBI | |
Wen Q, Liu J, Kang R, Zhou B and Tang D: The release and activity of HMGB1 in ferroptosis. Biochem Biophys Res Commun. 510:278–283. 2019. View Article : Google Scholar : PubMed/NCBI | |
Dai E, Han L, Liu J, Xie Y, Kroemer G, Klionsky DJ, Zeh HJ, Kang R, Wang J and Tang D: Autophagy-dependent ferroptosis drives tumor-associated macrophage polarization via release and uptake of oncogenic KRAS protein. Autophagy. 16:2069–2083. 2020. View Article : Google Scholar : PubMed/NCBI | |
Takei H, Araki A, Watanabe H, Ichinose A and Sendo F: Rapid killing of human neutrophils by the potent activator phorbol 12-myristate 13-acetate (PMA) accompanied by changes different from typical apoptosis or necrosis. J Leukoc Biol. 59:229–240. 1996. View Article : Google Scholar : PubMed/NCBI | |
Fuchs TA, Abed U, Goosmann C, Hurwitz R, Schulze I, Wahn V, Weinrauch Y, Brinkmann V and Zychlinsky A: Novel cell death program leads to neutrophil extracellular traps. J Cell Biol. 176:231–241. 2007. View Article : Google Scholar : PubMed/NCBI | |
Papayannopoulos V and Zychlinsky A: NETs: A new strategy for using old weapons. Trends Immunol. 30:513–521. 2009. View Article : Google Scholar : PubMed/NCBI | |
Monti M, De Rosa V, Iommelli F, Carriero MV, Terlizzi C, Camerlingo R, Di Minno G and Del Vecchio S: Neutrophil extracellular traps as an adhesion substrate for different tumor cells expressing RGD-Binding integrins. Int J Mol Sci. 19:23502018. View Article : Google Scholar : PubMed/NCBI | |
Pieterse E, Rother N, Garsen M, Hofstra JM, Satchell SC, Hoffmann M, Loeven MA, Knaapen HK, van der Heijden OWH, Berden JHM, et al: Neutrophil extracellular traps drive Endothelial-to-mesenchymal transition. Arterioscler Thromb Vasc Biol. 37:1371–1379. 2017. View Article : Google Scholar : PubMed/NCBI | |
Xiao Y, Cong M, Li J, He D, Wu Q, Tian P, Wang Y, Yang S, Liang C, Liang Y, et al: Cathepsin C promotes breast cancer lung metastasis by modulating neutrophil infiltration and neutrophil extracellular trap formation. Cancer Cell. 39:423–437.e7. 2021. View Article : Google Scholar : PubMed/NCBI | |
Xia X, Zhang Z, Zhu C, Ni B, Wang S, Yang S, Yu F, Zhao E, Li Q and Zhao G: Neutrophil extracellular traps promote metastasis in gastric cancer patients with postoperative abdominal infectious complications. Nat Commun. 13:10172022. View Article : Google Scholar : PubMed/NCBI | |
Awasthi D and Sarode A: Neutrophils at the crossroads: Unraveling the multifaceted role in the tumor microenvironment. Int J Mol Sci. 25:29292024. View Article : Google Scholar : PubMed/NCBI | |
Li C, Chen T, Liu J, Wang Y, Zhang C, Guo L, Shi D, Zhang T, Wang X and Li J: FGF19-induced inflammatory CAF promoted neutrophil extracellular trap formation in the liver metastasis of colorectal cancer. Adv Sci (Weinh). 10:e23026132023. View Article : Google Scholar : PubMed/NCBI | |
Yang L, Liu Q, Zhang X, Liu X, Zhou B, Chen J, Huang D, Li J, Li H, Chen F, et al: DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25. Nature. 583:133–138. 2020. View Article : Google Scholar : PubMed/NCBI | |
Lee W, Ko SY, Mohamed MS, Kenny HA, Lengyel E and Naora H: Neutrophils facilitate ovarian cancer premetastatic niche formation in the omentum. J Exp Med. 216:176–194. 2019. View Article : Google Scholar : PubMed/NCBI | |
Aldabbous L, Abdul-Salam V, McKinnon T, Duluc L, Pepke-Zaba J, Southwood M, Ainscough AJ, Hadinnapola C, Wilkins MR, Toshner M and Wojciak-Stothard B: Neutrophil extracellular traps promote angiogenesis: Evidence from vascular pathology in pulmonary hypertension. Arterioscler Thromb Vasc Biol. 36:2078–2087. 2016. View Article : Google Scholar : PubMed/NCBI | |
Zhang H, Wu D, Wang Y, Guo K, Spencer CB, Ortoga L, Qu M, Shi Y, Shao Y, Wang Z, et al: METTL3-mediated N6-methyladenosine exacerbates ferroptosis via m6A-IGF2BP2-dependent mitochondrial metabolic reprogramming in sepsis-induced acute lung injury. Clin Transl Med. 13:e13892023. View Article : Google Scholar : PubMed/NCBI | |
Zhang Y and Ertl HC: Starved and Asphyxiated: How Can CD8(+) T cells within a tumor microenvironment prevent tumor progression. Front Immunol. 7:322016. View Article : Google Scholar : PubMed/NCBI | |
Chen X, Song M, Zhang B and Zhang Y: Reactive oxygen species regulate T cell immune response in the tumor microenvironment. Oxid Med Cell Longev. 2016:15809672016. View Article : Google Scholar : PubMed/NCBI | |
Demers M, Krause DS, Schatzberg D, Martinod K, Voorhees JR, Fuchs TA, Scadden DT and Wagner DD: Cancers predispose neutrophils to release extracellular DNA traps that contribute to cancer-associated thrombosis. Proc Natl Acad Sci USA. 109:13076–13081. 2012. View Article : Google Scholar : PubMed/NCBI | |
Yao L, Sheng X, Dong X, Zhou W, Li Y, Ma X, Song Y, Dai H and Du Y: Neutrophil extracellular traps mediate TLR9/Merlin axis to resist ferroptosis and promote triple negative breast cancer progression. Apoptosis. 28:1484–1495. 2023. View Article : Google Scholar : PubMed/NCBI | |
Zhang W: The mitophagy receptor FUN14 domain-containing 1 (FUNDC1): A promising biomarker and potential therapeutic target of human diseases. Genes Dis. 8:640–654. 2021. View Article : Google Scholar : PubMed/NCBI | |
Al-Faze R, Ahmed HA, El-Atawy MA, Zagloul H, Alshammari EM, Jaremko M, Emwas AH, Nabil GM and Hanna DH: Mitochondrial dysfunction route as a possible biomarker and therapy target for human cancer. Biomed J. March 5–2024.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI | |
Sugioka R, Shimizu S and Tsujimoto Y: Fzo1, a protein involved in mitochondrial fusion, inhibits apoptosis. J Biol Chem. 279:52726–52734. 2004. View Article : Google Scholar : PubMed/NCBI | |
Chen QM: Nrf2 for protection against oxidant generation and mitochondrial damage in cardiac injury. Free Radic Biol Med. 179:133–143. 2022. View Article : Google Scholar : PubMed/NCBI | |
Tian C, Liu Y, Li Z, Zhu P and Zhao M: Mitochondria related cell death modalities and disease. Front Cell Dev Biol. 10:8323562022. View Article : Google Scholar : PubMed/NCBI | |
Li Y, Wang X, Huang Z, Zhou Y, Xia J, Hu W, Wang X, Du J, Tong X and Wang Y: CISD3 inhibition drives cystine-deprivation induced ferroptosis. Cell Death Dis. 12:8392021. View Article : Google Scholar : PubMed/NCBI | |
Yu F, Zhang Q, Liu H, Liu J, Yang S, Luo X, Liu W, Zheng H, Liu Q, Cui Y, et al: Dynamic O-GlcNAcylation coordinates ferritinophagy and mitophagy to activate ferroptosis. Cell Discov. 8:402022. View Article : Google Scholar : PubMed/NCBI | |
Yu Z, Cao W, Ren Y, Zhang Q and Liu J: ATPase copper transporter A, negatively regulated by miR-148a-3p, contributes to cisplatin resistance in breast cancer cells. Clin Transl Med. 10:57–73. 2020. View Article : Google Scholar : PubMed/NCBI | |
Finney L, Mandava S, Ursos L, Zhang W, Rodi D, Vogt S, Legnini D, Maser J, Ikpatt F and Olopade OI: X-ray fluorescence microscopy reveals large-scale relocalization and extracellular translocation of cellular copper during angiogenesis. Proc Natl Acad Sci USA. 104:2247–2252. 2007. View Article : Google Scholar : PubMed/NCBI | |
Lopez J, Ramchandani D and Vahdat L: Copper depletion as a therapeutic strategy in cancer. Met Ions Life Sci. 303–330. 2019.PubMed/NCBI | |
Shanbhag VC, Gudekar N, Jasmer K, Papageorgiou C, Singh K and Petris MJ: Copper metabolism as a unique vulnerability in cancer. Biochim Biophys Acta Mol Cell Res. 1868:1188932021. View Article : Google Scholar : PubMed/NCBI | |
Lossow K, Schwarz M and Kipp AP: Are trace element concentrations suitable biomarkers for the diagnosis of cancer? Redox Biol. 42:1019002021. View Article : Google Scholar : PubMed/NCBI | |
Chen L, Min J and Wang F: Copper homeostasis and cuproptosis in health and disease. Signal Transduct Target Ther. 7:3782022. View Article : Google Scholar : PubMed/NCBI | |
Tsvetkov P, Detappe A, Cai K, Keys HR, Brune Z, Ying W, Thiru P, Reidy M, Kugener G, Rossen J, et al: Mitochondrial metabolism promotes adaptation to proteotoxic stress. Nat Chem Biol. 15:681–689. 2019. View Article : Google Scholar : PubMed/NCBI | |
Mayr JA, Feichtinger RG, Tort F, Ribes A and Sperl W: Lipoic acid biosynthesis defects. J Inherit Metab Dis. 37:553–563. 2014. View Article : Google Scholar : PubMed/NCBI | |
Solmonson A and DeBerardinis RJ: Lipoic acid metabolism and mitochondrial redox regulation. J Biol Chem. 293:7522–7530. 2018. View Article : Google Scholar : PubMed/NCBI | |
Brewer GJ, Askari F, Lorincz MT, Carlson M, Schilsky M, Kluin KJ, Hedera P, Moretti P, Fink JK, Tankanow R, et al: Treatment of Wilson disease with ammonium tetrathiomolybdate: IV. Comparison of tetrathiomolybdate and trientine in a double-blind study of treatment of the neurologic presentation of Wilson disease. Arch Neurol. 63:521–527. 2006. View Article : Google Scholar : PubMed/NCBI | |
Chen T, Liang L, Wang Y, Li X and Yang C: Ferroptosis and cuproptposis in kidney diseases: Dysfunction of cell metabolism. Apoptosis. 29:289–302. 2024. View Article : Google Scholar : PubMed/NCBI | |
He B, Liao Y, Tian M, Tang C, Tang Q, Ma F, Zhou W, Leng Y and Zhong D: Identification and verification of a novel signature that combines cuproptosis-related genes with ferroptosis-related genes in osteoarthritis using bioinformatics analysis and experimental validation. Arthritis Res Ther. 26:1002024. View Article : Google Scholar : PubMed/NCBI | |
Luo G, Wang L, Zheng Z, Gao B and Lei C: Cuproptosis-related ferroptosis genes for predicting prognosis in kidney renal clear cell carcinoma. Eur J Med Res. 28:1762023. View Article : Google Scholar : PubMed/NCBI | |
Xue Q, Yan D, Chen X, Li X, Kang R, Klionsky DJ, Kroemer G, Chen X, Tang D and Liu J: Copper-dependent autophagic degradation of GPX4 drives ferroptosis. Autophagy. 19:1982–1996. 2023. View Article : Google Scholar : PubMed/NCBI | |
Xiong C, Ling H, Hao Q and Zhou X: Cuproptosis: A53-regulated metabolic cell death? Cell Death Differ. 30:876–884. 2023. View Article : Google Scholar : PubMed/NCBI | |
Shao L, Zhu L, Su R, Yang C, Gao X, Xu Y, Wang H, Guo C and Li H: Baicalin enhances the chemotherapy sensitivity of oxaliplatin-resistant gastric cancer cells by activating p53-mediated ferroptosis. Sci Rep. 14:107452024. View Article : Google Scholar : PubMed/NCBI | |
Zou Y, Palte MJ, Deik AA, Li H, Eaton JK, Wang W, Tseng YY, Deasy R, Kost-Alimova M, Dančík V, et al: A GPX4-dependent cancer cell state underlies the clear-cell morphology and confers sensitivity to ferroptosis. Nat Commun. 10:16172019. View Article : Google Scholar : PubMed/NCBI | |
Lu Y, Qin H, Jiang B, Lu W, Hao J, Cao W, Du L, Chen W, Zhao X, Guo H, et al: KLF2 inhibits cancer cell migration and invasion by regulating ferroptosis through GPX4 in clear cell renal cell carcinoma. Cancer Lett. 522:1–13. 2021. View Article : Google Scholar : PubMed/NCBI | |
Gradishar WJ, Moran MS, Abraham J, Aft R, Agnese D, Allison KH, Anderson B, Burstein HJ, Chew H, Dang C, et al: Breast cancer, version 3.2022, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 20:691–722. 2022. View Article : Google Scholar : PubMed/NCBI | |
Zou Y, Zheng S, Xie X, Ye F, Hu X, Tian Z, Yan SM, Yang L, Kong Y, Tang Y, et al: N6-methyladenosine regulated FGFR4 attenuates ferroptotic cell death in recalcitrant HER2-positive breast cancer. Nat Commun. 13:26722022. View Article : Google Scholar : PubMed/NCBI | |
Wu S, Pan R, Lu J, Wu X, Xie J, Tang H and Li X: Development and verification of a prognostic Ferroptosis-related gene model in triple-negative breast cancer. Front Oncol. 12:8969272022. View Article : Google Scholar : PubMed/NCBI | |
Zou Y, Yang A, Chen B, Deng X, Xie J, Dai D, Zhang J, Tang H, Wu T, Zhou Z, et al: crVDAC3 alleviates ferroptosis by impeding HSPB1 ubiquitination and confers trastuzumab deruxtecan resistance in HER2-low breast cancer. Drug Resist Updat. 77:1011262024. View Article : Google Scholar : PubMed/NCBI | |
Giordano C, Chemi F, Panza S, Barone I, Bonofiglio D, Lanzino M, Cordella A, Campana A, Hashim A, Rizza P, et al: Leptin as a mediator of tumor-stromal interactions promotes breast cancer stem cell activity. Oncotarget. 7:1262–1275. 2016. View Article : Google Scholar : PubMed/NCBI | |
Balaban S, Shearer RF, Lee LS, van Geldermalsen M, Schreuder M, Shtein HC, Cairns R, Thomas KC, Fazakerley DJ, Grewal T, et al: Adipocyte lipolysis links obesity to breast cancer growth: Adipocyte-derived fatty acids drive breast cancer cell proliferation and migration. Cancer Metab. 5:12017. View Article : Google Scholar : PubMed/NCBI | |
He JY, Wei XH, Li SJ, Liu Y, Hu HL, Li ZZ, Kuang XH, Wang L, Shi X, Yuan ST and Sun L: Adipocyte-derived IL-6 and leptin promote breast Cancer metastasis via upregulation of Lysyl Hydroxylase-2 expression. Cell Commun Signal. 16:1002018. View Article : Google Scholar : PubMed/NCBI | |
Koundouros N and Poulogiannis G: Reprogramming of fatty acid metabolism in cancer. Br J Cancer. 122:4–22. 2020. View Article : Google Scholar : PubMed/NCBI | |
Bobiński R, Dutka M, Pizon M, Waksmańska W and Pielesz A: Ferroptosis, Acyl starvation, and breast cancer. Mol Pharmacol. 103:132–144. 2023. View Article : Google Scholar : PubMed/NCBI | |
Pondé NF, Zardavas D and Piccart M: Progress in adjuvant systemic therapy for breast cancer. Nat Rev Clin Oncol. 16:27–44. 2019. View Article : Google Scholar : PubMed/NCBI | |
Bi M, Zhang Z, Jiang YZ, Xue P, Wang H, Lai Z, Fu X, De Angelis C, Gong Y, Gao Z, et al: Enhancer reprogramming driven by high-order assemblies of transcription factors promotes phenotypic plasticity and breast cancer endocrine resistance. Nat Cell Biol. 22:701–715. 2020. View Article : Google Scholar : PubMed/NCBI | |
Xu Z, Wang X, Sun W, Xu F, Kou H, Hu W, Zhang Y, Jiang Q, Tang J and Xu Y: RelB-activated GPX4 inhibits ferroptosis and confers tamoxifen resistance in breast cancer. Redox Biol. 68:1029522023. View Article : Google Scholar : PubMed/NCBI | |
He HL, Lee YE, Chen HP, Hsing CH, Chang IW, Shiue YL, Lee SW, Hsu CT, Lin LC, Wu TF and Li CF: Overexpression of DNAJC12 predicts poor response to neoadjuvant concurrent chemoradiotherapy in patients with rectal cancer. Exp Mol Pathol. 98:338–345. 2015. View Article : Google Scholar : PubMed/NCBI | |
Shen M, Cao S, Long X, Xiao L, Yang L, Zhang P, Li L, Chen F, Lei T, Gao H, et al: DNAJC12 causes breast cancer chemotherapy resistance by repressing doxorubicin-induced ferroptosis and apoptosis via activation of AKT. Redox Biol. 70:1030352024. View Article : Google Scholar : PubMed/NCBI | |
Bianchini G, Balko JM, Mayer IA, Sanders ME and Gianni L: Triple-negative breast cancer: Challenges and opportunities of a heterogeneous disease. Nat Rev Clin Oncol. 13:674–690. 2016. View Article : Google Scholar : PubMed/NCBI | |
Denkert C, Liedtke C, Tutt A and von Minckwitz G: Molecular alterations in triple-negative breast cancer-the road to new treatment strategies. Lancet. 389:2430–2442. 2017. View Article : Google Scholar : PubMed/NCBI | |
Xiao Y, Ma D, Zhao S, Suo C, Shi J, Xue MZ, Ruan M, Wang H, Zhao J, Li Q, et al: Multi-Omics Profiling reveals distinct microenvironment characterization and suggests immune escape mechanisms of Triple-negative breast cancer. Clin Cancer Res. 25:5002–5014. 2019. View Article : Google Scholar : PubMed/NCBI | |
Yu H, Yang C, Jian L, Guo S, Chen R, Li K, Qu F, Tao K, Fu Y, Luo F and Liu S: Sulfasalazine-induced ferroptosis in breast cancer cells is reduced by the inhibitory effect of estrogen receptor on the transferrin receptor. Oncol Rep. 42:826–838. 2019.PubMed/NCBI | |
Timmerman LA, Holton T, Yuneva M, Louie RJ, Padró M, Daemen A, Hu M, Chan DA, Ethier SP, van ‘t Veer LJ, et al: Glutamine sensitivity analysis identifies the xCT antiporter as a common triple-negative breast tumor therapeutic target. Cancer Cell. 24:450–465. 2013. View Article : Google Scholar : PubMed/NCBI | |
Wang Z, Dong J, Tian W, Qiao S and Wang H: Role of TRPV1 ion channel in cervical squamous cell carcinoma genesis. Front Mol Biosci. 9:9802622022. View Article : Google Scholar : PubMed/NCBI | |
Liu Y, Li L, Yang Z, Wen D and Hu Z: Circular RNA circACAP2 suppresses ferroptosis of cervical cancer during malignant progression by miR-193a-5p/GPX4. J Oncol. 2022:52288742022.PubMed/NCBI | |
Wu P, Li C, Ye DM, Yu K, Li Y, Tang H, Xu G, Yi S and Zhang Z: Circular RNA circEPSTI1 accelerates cervical cancer progression via miR-375/409-3P/515-5p-SLC7A11 axis. Aging (Albany NY). 13:4663–4673. 2021. View Article : Google Scholar : PubMed/NCBI | |
Xiong J, Nie M, Fu C, Chai X, Zhang Y, He L and Sun S: Hypoxia enhances HIF1α transcription activity by Upregulating KDM4A and mediating H3K9me3, thus inducing ferroptosis resistance in cervical cancer cells. Stem Cells Int. 2022:16088062022. View Article : Google Scholar : PubMed/NCBI | |
Wu Y, Fang B, Yang XQ, Wang L, Chen D, Krasnykh V, Carter BZ, Morris JS and Shureiqi I: Therapeutic molecular targeting of 15-lipoxygenase-1 in colon cancer. Mol Ther. 16:886–892. 2008. View Article : Google Scholar | |
Abdurahman A, Li Y, Jia SZ, Xu XW, Lin SJ, Ouyang P, Jun He Z, Zhang ZH, Liu Q, Xu Y and Song GL: Knockdown of the SELENOK gene induces ferroptosis in cervical cancer cells. Metallomics. 15:mfad0192023. View Article : Google Scholar : PubMed/NCBI | |
Ray Chaudhuri A and Nussenzweig A: The multifaceted roles of PARP1 in DNA repair and chromatin remodelling. Nat Rev Mol Cell Biol. 18:610–621. 2017. View Article : Google Scholar : PubMed/NCBI | |
Sánchez-Quesada C, López-Biedma A and Gaforio JJ: Oleanolic acid, a compound present in grapes and olives, protects against genotoxicity in human mammary epithelial cells. Molecules. 20:13670–13688. 2015. View Article : Google Scholar : PubMed/NCBI | |
Shi H, Xiong L, Yan G, Du S, Liu J and Shi Y: Susceptibility of cervical cancer to dihydroartemisinin-induced ferritinophagy-dependent ferroptosis. Front Mol Biosci. 10:11560622023. View Article : Google Scholar : PubMed/NCBI | |
Liu S, Zhang HL, Li J, Ye ZP, Du T, Li LC, Guo YQ, Yang D, Li ZL, Cao JH, et al: Tubastatin A potently inhibits GPX4 activity to potentiate cancer radiotherapy through boosting ferroptosis. Redox Biol. 62:1026772023. View Article : Google Scholar : PubMed/NCBI | |
Lei G, Zhang Y, Koppula P, Liu X, Zhang J, Lin SH, Ajani JA, Xiao Q, Liao Z, Wang H and Gan B: The role of ferroptosis in ionizing radiation-induced cell death and tumor suppression. Cell Res. 30:146–162. 2020. View Article : Google Scholar : PubMed/NCBI | |
Lheureux S, Gourley C, Vergote I and Oza AM: Epithelial ovarian cancer. Lancet. 393:1240–1253. 2019. View Article : Google Scholar : PubMed/NCBI | |
Zhang J, Ouyang F, Gao A, Zeng T, Li M, Li H, Zhou W, Gao Q, Tang X, Zhang Q, et al: ESM1 enhances fatty acid synthesis and vascular mimicry in ovarian cancer by utilizing the PKM2-dependent Warburg effect within the hypoxic tumor microenvironment. Mol Cancer. 23:942024. View Article : Google Scholar : PubMed/NCBI | |
Fan Z, Ye M, Liu D, Zhou W, Zeng T, He S and Li Y: Lactate drives the ESM1-SCD1 axis to inhibit the antitumor CD8+ T-cell response by activating the Wnt/β-catenin pathway in ovarian cancer cells and inducing cisplatin resistance. Int Immunopharmacol. 137:1124612024. View Article : Google Scholar : PubMed/NCBI | |
Li YK, Gao AB, Zeng T, Liu D, Zhang QF, Ran XM, Tang ZZ, Li Y, Liu J, Zhang T, et al: ANGPTL4 accelerates ovarian serous cystadenocarcinoma carcinogenesis and angiogenesis in the tumor microenvironment by activating the JAK2/STAT3 pathway and interacting with ESM1. J Transl Med. 22:462024. View Article : Google Scholar : PubMed/NCBI | |
Christie EL and Bowtell DDL: Acquired chemotherapy resistance in ovarian cancer. Ann Oncol. 28 (Suppl_8):viii13–viii5. 2017. View Article : Google Scholar : PubMed/NCBI | |
Ruan D, Wen J, Fang F, Lei Y, Zhao Z and Miao Y: Ferroptosis in epithelial ovarian cancer: A burgeoning target with extraordinary therapeutic potential. Cell Death Discov. 9:4342023. View Article : Google Scholar : PubMed/NCBI | |
Fu R, Zhao B, Chen M, Fu X, Zhang Q, Cui Y, Fu X, Li R, Zhong G and Zhou X: Moving beyond cisplatin resistance: mechanisms, challenges, and prospects for overcoming recurrence in clinical cancer therapy. Med Oncol. 41:92023. View Article : Google Scholar : PubMed/NCBI | |
Lv C, Qu H, Zhu W, Xu K, Xu A, Jia B, Qing Y, Li H, Wei HJ and Zhao HY: Low-dose paclitaxel inhibits tumor cell growth by regulating glutaminolysis in colorectal carcinoma cells. Front Pharmacol. 8:2442017. View Article : Google Scholar : PubMed/NCBI | |
Wang Y, Zhao G, Condello S, Huang H, Cardenas H, Tanner EJ, Wei J, Ji Y, Li J, Tan Y, et al: Frizzled-7 identifies platinum-tolerant ovarian cancer cells susceptible to ferroptosis. Cancer Res. 81:384–399. 2021. View Article : Google Scholar : PubMed/NCBI | |
Shi M, Zhang MJ, Yu Y, Ou R, Wang Y, Li H and Ge RS: Curcumin derivative NL01 induces ferroptosis in ovarian cancer cells via HCAR1/MCT1 signaling. Cell Signal. 109:1107912023. View Article : Google Scholar : PubMed/NCBI | |
Cheng Q, Bao L, Li M, Chang K and Yi X: Erastin synergizes with cisplatin via ferroptosis to inhibit ovarian cancer growth in vitro and in vivo. J Obstet Gynaecol Res. 47:2481–2491. 2021. View Article : Google Scholar : PubMed/NCBI | |
Ni M, Zhou J, Zhu Z, Xu Q, Yin Z, Wang Y, Zheng Z and Zhao H: Shikonin and cisplatin synergistically overcome cisplatin resistance of ovarian cancer by inducing ferroptosis via upregulation of HMOX1 to promote Fe2+ accumulation. Phytomedicine. 112:1547012023. View Article : Google Scholar : PubMed/NCBI | |
Krishnakumar R and Kraus WL: The PARP side of the nucleus: Molecular actions, physiological outcomes, and clinical targets. Mol Cell. 39:8–24. 2010. View Article : Google Scholar : PubMed/NCBI | |
Gibson BA and Kraus WL: New insights into the molecular and cellular functions of poly(ADP-ribose) and PARPs. Nat Rev Mol Cell Biol. 13:411–424. 2012. View Article : Google Scholar : PubMed/NCBI | |
Audeh MW, Carmichael J, Penson RT, Friedlander M, Powell B, Bell-McGuinn KM, Scott C, Weitzel JN, Oaknin A, Loman N, et al: Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: A proof-of-concept trial. Lancet. 376:245–251. 2010. View Article : Google Scholar : PubMed/NCBI | |
Alsop K, Fereday S, Meldrum C, deFazio A, Emmanuel C, George J, Dobrovic A, Birrer MJ, Webb PM, Stewart C, et al: BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: A report from the Australian Ovarian Cancer Study Group. J Clin Oncol. 30:2654–2663. 2012. View Article : Google Scholar : PubMed/NCBI | |
Hong T, Lei G, Chen X, Li H, Zhang X, Wu N, Zhao Y, Zhang Y and Wang J: PARP inhibition promotes ferroptosis via repressing SLC7A11 and synergizes with ferroptosis inducers in BRCA-proficient ovarian cancer. Redox Biol. 42:1019282021. View Article : Google Scholar : PubMed/NCBI | |
Tang S, Shen Y, Wei X, Shen Z, Lu W and Xu J: Olaparib synergizes with arsenic trioxide by promoting apoptosis and ferroptosis in platinum-resistant ovarian cancer. Cell Death Dis. 13:8262022. View Article : Google Scholar : PubMed/NCBI | |
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021. View Article : Google Scholar : PubMed/NCBI | |
Fang X, Zhang T and Chen Z: Solute carrier family 7 member 11 (SLC7A11) is a potential prognostic biomarker in uterine corpus endometrial carcinoma. Int J Gen Med. 16:481–497. 2023. View Article : Google Scholar : PubMed/NCBI | |
Marshall AD, van Geldermalsen M, Otte NJ, Lum T, Vellozzi M, Thoeng A, Pang A, Nagarajah R, Zhang B, Wang Q, et al: ASCT2 regulates glutamine uptake and cell growth in endometrial carcinoma. Oncogenesis. 6:e3672017. View Article : Google Scholar : PubMed/NCBI | |
Liu X, Olszewski K, Zhang Y, Lim EW, Shi J, Zhang X, Zhang J, Lee H, Koppula P, Lei G, et al: Cystine transporter regulation of pentose phosphate pathway dependency and disulfide stress exposes a targetable metabolic vulnerability in cancer. Nat Cell Biol. 22:476–486. 2020. View Article : Google Scholar : PubMed/NCBI | |
Byrne FL, Poon IK, Modesitt SC, Tomsig JL, Chow JD, Healy ME, Baker WD, Atkins KA, Lancaster JM, Marchion DC, et al: Metabolic vulnerabilities in endometrial cancer. Cancer Res. 74:5832–5845. 2014. View Article : Google Scholar : PubMed/NCBI | |
Han X, Ren C, Yang T, Qiao P, Wang L, Jiang A, Meng Y, Liu Z, Du Y and Yu Z: Negative regulation of AMPKα1 by PIM2 promotes aerobic glycolysis and tumorigenesis in endometrial cancer. Oncogene. 38:6537–6549. 2019. View Article : Google Scholar : PubMed/NCBI | |
Cheng H, Jiang XY, Zheng RR, Zuo SJ, Zhao LP, Fan GL, Xie BR, Yu XY, Li SY and Zhang XZ: A biomimetic cascade nanoreactor for tumor targeted starvation therapy-amplified chemotherapy. Biomaterials. 195:75–85. 2019. View Article : Google Scholar : PubMed/NCBI | |
Yu S, Chen Z, Zeng X, Chen X and Gu Z: Advances in nanomedicine for cancer starvation therapy. Theranostics. 9:8026–8047. 2019. View Article : Google Scholar : PubMed/NCBI | |
Murakami H, Hayashi M, Terada S and Ohmichi M: Medroxyprogesterone acetate-resistant endometrial cancer cells are susceptible to ferroptosis inducers. Life Sci. 325:1217532023. View Article : Google Scholar : PubMed/NCBI | |
Zhang YY, Ni ZJ, Elam E, Zhang F, Thakur K, Wang S, Zhang JG and Wei ZJ: Juglone, a novel activator of ferroptosis, induces cell death in endometrial carcinoma Ishikawa cells. Food Funct. 12:4947–4959. 2021. View Article : Google Scholar : PubMed/NCBI | |
Hua Y, Yang S, Zhang Y, Li J, Wang M, Yeerkenbieke P, Liao Q and Liu Q: Modulating ferroptosis sensitivity: Environmental and cellular targets within the tumor microenvironment. J Exp Clin Cancer Res. 43:192024. View Article : Google Scholar : PubMed/NCBI | |
Hu Y, Wang H and Liu Y: NETosis: Sculpting tumor metastasis and immunotherapy. Immunol Rev. 321:263–279. 2024. View Article : Google Scholar : PubMed/NCBI | |
Zhang H, Liu J, Zhou Y, Qu M, Wang Y, Guo K, Shen R, Sun Z, Cata JP, Yang S, et al: Neutrophil extracellular traps mediate m6A modification and regulates sepsis-associated acute lung injury by activating ferroptosis in alveolar epithelial cells. Int J Biol Sci. 18:3337–3357. 2022. View Article : Google Scholar : PubMed/NCBI | |
Chu C, Wang X, Yang C, Chen F, Shi L, Xu W, Wang K, Liu B, Wang C, Sun D and Ding W: Neutrophil extracellular traps drive intestinal microvascular endothelial ferroptosis by impairing Fundc1-dependent mitophagy. Redox Biol. 67:1029062023. View Article : Google Scholar : PubMed/NCBI | |
Medlock AE, Hixon JC, Bhuiyan T and Cobine PA: Prime real estate: Metals, cofactors and MICOS. Front Cell Dev Biol. 10:8923252022. View Article : Google Scholar : PubMed/NCBI | |
Xie J, Yang Y, Gao Y and He J: Cuproptosis: Mechanisms and links with cancers. Mol Cancer. 22:462023. View Article : Google Scholar : PubMed/NCBI | |
Wang W, Lu K, Jiang X, Wei Q, Zhu L, Wang X, Jin H and Feng L: Ferroptosis inducers enhanced cuproptosis induced by copper ionophores in primary liver cancer. J Exp Clin Cancer Res. 42:1422023. View Article : Google Scholar : PubMed/NCBI | |
Li Y, Du Y, Zhou Y, Chen Q, Luo Z, Ren Y, Chen X and Chen G: Iron and copper: Critical executioners of ferroptosis, cuproptosis and other forms of cell death. Cell Commun Signal. 21:3272023. View Article : Google Scholar : PubMed/NCBI | |
Liu T, Liu W, Zhang M, Yu W, Gao F, Li C, Wang SB, Feng J and Zhang XZ: Ferrous-supply-regeneration nanoengineering for cancer-cell-specific ferroptosis in combination with imaging-guided photodynamic therapy. ACS Nano. 12:12181–12192. 2018. View Article : Google Scholar : PubMed/NCBI | |
Dixon SJ, Patel DN, Welsch M, Skouta R, Lee ED, Hayano M, Thomas AG, Gleason CE, Tatonetti NP, Slusher BS and Stockwell BR: Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis. Elife. 3:e025232014. View Article : Google Scholar : PubMed/NCBI | |
Liang C, Zhang X, Yang M and Dong X: Recent progress in ferroptosis inducers for cancer therapy. Adv Mater. 31:e19041972019. View Article : Google Scholar : PubMed/NCBI | |
Yang J, Jia Z, Zhang J, Pan X, Wei Y, Ma S, Yang N, Liu Z and Shen Q: Metabolic intervention nanoparticles for triple-negative breast cancer therapy via overcoming FSP1-mediated ferroptosis resistance. Adv Healthc Mater. 11:e21027992022. View Article : Google Scholar : PubMed/NCBI | |
Radadiya PS, Thornton MM, Puri RV, Yerrathota S, Dinh-Phan J, Magenheimer B, Subramaniam D, Tran PV, Zhu H, Bolisetty S, et al: Ciclopirox olamine induces ferritinophagy and reduces cyst burden in polycystic kidney disease. JCI Insight. 6:e1412992021. View Article : Google Scholar : PubMed/NCBI | |
Yao X, Zhang Y, Hao J, Duan HQ, Zhao CX, Sun C, Li B, Fan BY, Wang X, Li WX, et al: Deferoxamine promotes recovery of traumatic spinal cord injury by inhibiting ferroptosis. Neural Regen Res. 14:532–541. 2019. View Article : Google Scholar : PubMed/NCBI | |
Zheng H, Jiang J, Xu S, Liu W, Xie Q, Cai X, Zhang J, Liu S and Li R: Nanoparticle-induced ferroptosis: Detection methods, mechanisms and applications. Nanoscale. 13:2266–2285. 2021. View Article : Google Scholar : PubMed/NCBI | |
Brown CW, Amante JJ, Chhoy P, Elaimy AL, Liu H, Zhu LJ, Baer CE, Dixon SJ and Mercurio AM: Prominin2 drives ferroptosis resistance by stimulating iron export. Dev Cell. 51:575–586.e4. 2019. View Article : Google Scholar : PubMed/NCBI | |
Wu H and Liu A: Long non-coding RNA NEAT1 regulates ferroptosis sensitivity in non-small-cell lung cancer. J Int Med Res. 49:3000605219961832021. View Article : Google Scholar : PubMed/NCBI | |
Alim I, Caulfield JT, Chen Y, Swarup V, Geschwind DH, Ivanova E, Seravalli J, Ai Y, Sansing LH, Ste Marie EJ, et al: Selenium drives a transcriptional adaptive program to block ferroptosis and treat stroke. Cell. 177:1262–1279.e25. 2019. View Article : Google Scholar : PubMed/NCBI |