Potential of lactylation as a therapeutic target in cancer treatment (Review)
- Authors:
- Zhengfeng Zhu
- Xinzhe Zheng
- Pengfei Zhao
- Cheng Chen
- Gang Xu
- Xixian Ke
-
Affiliations: Department of Clinical Medicine, Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China, Department of Thoracic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China - Published online on: February 7, 2025 https://doi.org/10.3892/mmr.2025.13456
- Article Number: 91
-
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
Abstract
 |
 |
|
Doyle HA and Mamula MJ: Post-translational protein modifications in antigen recognition and autoimmunity. Trends Immunol. 22:443–449. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Ramazi S and Zahiri J: Posttranslational modifications in proteins: Resources, tools and prediction methods. Database (Oxford). 2021:baab0122021. View Article : Google Scholar : PubMed/NCBI | |
|
Wang H, Yang L, Liu M and Luo J: Protein post-translational modifications in the regulation of cancer hallmarks. Cancer Gene Ther. 30:529–547. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang H and Han W: Protein post-translational modifications in head and neck cancer. Front Oncol. 10:5719442020. View Article : Google Scholar : PubMed/NCBI | |
|
Visconti A and Qiu H: Recent advances in serum response factor posttranslational modifications and their therapeutic potential in cardiovascular and neurological diseases. Vascul Pharmacol. 156:1074212024. View Article : Google Scholar : PubMed/NCBI | |
|
Wang Z, Li M, Jiang H, Luo S, Shao F, Xia Y, Yang M, Ren X, Liu T, Yan M, et al: Fructose-1,6-bisphosphatase 1 functions as a protein phosphatase to dephosphorylate histone H3 and suppresses PPARα-regulated gene transcription and tumour growth. Nat Cell Biol. 24:1655–1665. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Zhong Q, Xiao X, Qiu Y, Xu Z, Chen C, Chong B, Zhao X, Hai S, Li S, An Z and Dai L: Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications. MedComm (2020). 4:e2612023. View Article : Google Scholar : PubMed/NCBI | |
|
Yu T, Wang Y, Fan Y, Fang N, Wang T, Xu T and Shu Y: CircRNAs in cancer metabolism: A review. J Hematol Oncol. 12:902019. View Article : Google Scholar : PubMed/NCBI | |
|
San-Millan I, Sparagna GC, Chapman HL, Warkins VL, Chatfield KC, Shuff SR, Martinez JL and Brooks GA: Chronic lactate exposure decreases mitochondrial function by inhibition of fatty acid uptake and cardiolipin alterations in neonatal rat cardiomyocytes. Front Nutr. 9:8094852022. View Article : Google Scholar : PubMed/NCBI | |
|
Brooks GA: Lactate as a fulcrum of metabolism. Redox Biol. 35:1014542020. View Article : Google Scholar : PubMed/NCBI | |
|
Zhu W, Guo S, Sun J, Zhao Y and Liu C: Lactate and lactylation in cardiovascular diseases: Current progress and future perspectives. Metabolism. 158:1559572024. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang D, Tang Z, Huang H, Zhou G, Cui C, Weng Y, Liu W, Kim S, Lee S, Perez-Neut M, et al: Metabolic regulation of gene expression by histone lactylation. Nature. 574:575–580. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Pérez-Tomás R and Pérez-Guillén I: Lactate in the tumor microenvironment: An essential molecule in cancer progression and treatment. Cancers (Basel). 12:32442020. View Article : Google Scholar : PubMed/NCBI | |
|
Yu X, Yang J, Xu J, Pan H, Wang W, Yu X and Shi S: Histone lactylation: From tumor lactate metabolism to epigenetic regulation. Int J Biol Sci. 20:1833–1854. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Heydari Z, Moeinvaziri F, Mirazimi SMA, Dashti F, Smirnova O, Shpichka A, Mirzaei H, Timashev P and Vosough M: Alteration in DNA methylation patterns: Epigenetic signatures in gastrointestinal cancers. Eur J Pharmacol. 973:1765632024. View Article : Google Scholar : PubMed/NCBI | |
|
Rungratanawanich W, Ballway JW, Wang X, Won KJ, Hardwick JP and Song BJ: Post-translational modifications of histone and non-histone proteins in epigenetic regulation and translational applications in alcohol-associated liver disease: Challenges and research opportunities. Pharmacol Ther. 251:1085472023. View Article : Google Scholar : PubMed/NCBI | |
|
Wang J, Wang Z, Wang Q, Li X and Guo Y: Ubiquitous protein lactylation in health and diseases. Cell Mol Biol Lett. 29:232024. View Article : Google Scholar : PubMed/NCBI | |
|
Xu X, Zhang DD, Kong P, Gao YK, Huang XF, Song Y, Zhang WD, Guo RJ, Li CL, Chen BW, et al: Sox10 escalates vascular inflammation by mediating vascular smooth muscle cell transdifferentiation and pyroptosis in neointimal hyperplasia. Cell Rep. 42:1128692023. View Article : Google Scholar : PubMed/NCBI | |
|
Yang D, Yin J, Shan L, Yi X, Zhang W and Ding Y: Identification of lysine-lactylated substrates in gastric cancer cells. iScience. 25:1046302022. View Article : Google Scholar : PubMed/NCBI | |
|
Chen M, Cen K, Song Y, Zhang X, Liou YC, Liu P, Huang J, Ruan J, He J, Ye W, et al: NUSAP1-LDHA-glycolysis-lactate feedforward loop promotes Warburg effect and metastasis in pancreatic ductal adenocarcinoma. Cancer Lett. 567:2162852023. View Article : Google Scholar : PubMed/NCBI | |
|
Meng Q, Sun H, Zhang Y, Yang X, Hao S, Liu B, Zhou H, Xu ZX and Wang Y: Lactylation stabilizes DCBLD1 activating the pentose phosphate pathway to promote cervical cancer progression. J Exp Clin Cancer Res. 43:362024. View Article : Google Scholar : PubMed/NCBI | |
|
Chu YD, Cheng LC, Lim SN, Lai MW, Yeh CT and Lin WR: Aldolase B-driven lactagenesis and CEACAM6 activation promote cell renewal and chemoresistance in colorectal cancer through the Warburg effect. Cell Death Dis. 14:6602023. View Article : Google Scholar : PubMed/NCBI | |
|
Gu X, Zhuang A, Yu J, Yang L, Ge S, Ruan J, Jia R, Fan X and Chai P: Histone lactylation-boosted ALKBH3 potentiates tumor progression and diminished promyelocytic leukemia protein nuclear condensates by m1A demethylation of SP100A. Nucleic Acids Res. 52:2273–2289. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Liu R, Wu J, Guo H, Yao W, Li S, Lu Y, Jia Y, Liang X, Tang J and Zhang H: Post-translational modifications of histones: Mechanisms, biological functions, and therapeutic targets. MedComm (2020). 4:e2922023. View Article : Google Scholar : PubMed/NCBI | |
|
Pan RY, He L, Zhang J, Liu X, Liao Y, Gao J, Liao Y, Yan Y, Li Q, Zhou X, et al: Positive feedback regulation of microglial glucose metabolism by histone H4 lysine 12 lactylation in Alzheimer's disease. Cell Metab. 34:634–648.e6. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Levine AJ and Puzio-Kuter AM: The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes. Science. 330:1340–1344. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang Y, Song H, Li M and Lu P: Histone lactylation bridges metabolic reprogramming and epigenetic rewiring in driving carcinogenesis: Oncometabolite fuels oncogenic transcription. Clin Transl Med. 14:e16142024. View Article : Google Scholar : PubMed/NCBI | |
|
Hu Y, He Z, Li Z, Wang Y, Wu N, Sun H, Zhou Z, Hu Q and Cong X: Lactylation: The novel histone modification influence on gene expression, protein function, and disease. Clin Epigenetics. 16:722024. View Article : Google Scholar : PubMed/NCBI | |
|
Wu D, Spencer CB, Ortoga L, Zhang H and Miao C: Histone lactylation-regulated METTL3 promotes ferroptosis via m6A-modification on ACSL4 in sepsis-associated lung injury. Redox Biol. 74:1031942024. View Article : Google Scholar : PubMed/NCBI | |
|
Wu F, Hua Y, Kaochar S, Nie S, Lin YL, Yao Y, Wu J, Wu X, Fu X, Schiff R, et al: Discovery, structure-activity relationship, and biological activity of histone-competitive inhibitors of histone acetyltransferases P300/CBP. J Med Chem. 63:4716–4731. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Antika TR, Chrestella DJ, Tseng YK, Yeh YH, Hsiao CD and Wang CC: A naturally occurring mini-alanyl-tRNA synthetase. Commun Biol. 6:3142023. View Article : Google Scholar : PubMed/NCBI | |
|
Zong Z, Xie F, Wang S, Wu X, Zhang Z, Yang B and Zhou F: Alanyl-tRNA synthetase, AARS1, is a lactate sensor and lactyltransferase that lactylates p53 and contributes to tumorigenesis. Cell. 187:2375–2392.e33. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Ju J, Zhang H, Lin M, Yan Z, An L, Cao Z, Geng D, Yue J, Tang Y, Tian L, et al: The alanyl-tRNA synthetase AARS1 moonlights as a lactyltransferase to promote YAP signaling in gastric cancer. J Clin Invest. 134:e1745872024. View Article : Google Scholar : PubMed/NCBI | |
|
Yoo L, Mendoza D, Richard AJ and Stephens JM: KAT8 beyond acetylation: A survey of its epigenetic regulation, genetic variability, and implications for human health. Genes (Basel). 15:6392024. View Article : Google Scholar : PubMed/NCBI | |
|
Xie B, Zhang M, Li J, Cui J, Zhang P, Liu F, Wu Y, Deng W, Ma J, Li X, et al: KAT8-catalyzed lactylation promotes eEF1A2-mediated protein synthesis and colorectal carcinogenesis. Proc Natl Acad Sci USA. 121:e23141281212024. View Article : Google Scholar : PubMed/NCBI | |
|
Dong H, Zhang J, Zhang H, Han Y, Lu C, Chen C, Tan X, Wang S, Bai X, Zhai G, et al: YiaC and CobB regulate lysine lactylation in Escherichia coli. Nat Commun. 13:66282022. View Article : Google Scholar : PubMed/NCBI | |
|
Parks AR and Escalante-Semerena JC: Modulation of the bacterial CobB sirtuin deacylase activity by N-terminal acetylation. Proc Natl Acad Sci USA. 117:15895–15901. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Mutlu B and Puigserver P: GCN5 acetyltransferase in cellular energetic and metabolic processes. Biochim Biophys Acta Gene Regul Mech. 1864:1946262021. View Article : Google Scholar : PubMed/NCBI | |
|
Yang K, Fan M, Wang X, Xu J, Wang Y, Tu F, Gill PS, Ha T, Liu L, Williams DL and Li C: Lactate promotes macrophage HMGB1 lactylation, acetylation, and exosomal release in polymicrobial sepsis. Cell Death Differ. 29:133–146. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Moreno-Yruela C, Zhang D, Wei W, Bæk M, Liu W, Gao J, Danková D, Nielsen AL, Bolding JE, Yang L, et al: Class I histone deacetylases (HDAC1-3) are histone lysine delactylases. Sci Adv. 8:eabi66962022. View Article : Google Scholar : PubMed/NCBI | |
|
Micelli C and Rastelli G: Histone deacetylases: Structural determinants of inhibitor selectivity. Drug Discov Today. 20:718–735. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Fan Z, Liu Z, Zhang N, Wei W, Cheng K, Sun H and Hao Q: Identification of SIRT3 as an eraser of H4K16la. iScience. 26:1077572023. View Article : Google Scholar : PubMed/NCBI | |
|
Tao Z, Jin Z, Wu J, Cai G and Yu X: Sirtuin family in autoimmune diseases. Front Immunol. 14:11862312023. View Article : Google Scholar : PubMed/NCBI | |
|
Hagihara H, Shoji H, Otabi H, Toyoda A, Katoh K, Namihira M and Miyakawa T: Protein lactylation induced by neural excitation. Cell Rep. 37:1098202021. View Article : Google Scholar : PubMed/NCBI | |
|
Rho H, Terry AR, Chronis C and Hay N: Hexokinase 2-mediated gene expression via histone lactylation is required for hepatic stellate cell activation and liver fibrosis. Cell Metab. 35:1406–1423.e8. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Gaffney DO, Jennings EQ, Anderson CC, Marentette JO, Shi T, Schou Oxvig AM, Streeter MD, Johannsen M, Spiegel DA, Chapman E, et al: Non-enzymatic lysine lactoylation of glycolytic enzymes. Cell Chem Biol. 27:206–213.e6. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Kiri S and Ryba T: Cancer, metastasis, and the epigenome. Mol Cancer. 23:1542024. View Article : Google Scholar : PubMed/NCBI | |
|
Lv X, Lv Y and Dai X: Lactate, histone lactylation and cancer hallmarks. Expert Rev Mol. 25:e72023. View Article : Google Scholar : PubMed/NCBI | |
|
Yan F, Teng Y, Li X, Zhong Y, Li C, Yan F and He X: Hypoxia promotes non-small cell lung cancer cell stemness, migration, and invasion via promoting glycolysis by lactylation of SOX9. Cancer Biol Ther. 25:23041612024. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang C, Zhou L, Zhang M, Du Y, Li C, Ren H and Zheng L: H3K18 lactylation potentiates immune escape of non-small cell lung cancer. Cancer Res. 84:3589–3601. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Qiao Z, Li Y, Li S, Liu S and Cheng Y: Hypoxia-induced SHMT2 protein lactylation facilitates glycolysis and stemness of esophageal cancer cells. Mol Cell Biochem. 479:3063–3076. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Miao Z, Zhao X and Liu X: Hypoxia induced β-catenin lactylation promotes the cell proliferation and stemness of colorectal cancer through the wnt signaling pathway. Exp Cell Res. 422:1134392023. View Article : Google Scholar : PubMed/NCBI | |
|
Yu J, Chai P, Xie M, Ge S, Ruan J, Fan X and Jia R: Histone lactylation drives oncogenesis by facilitating m6A reader protein YTHDF2 expression in ocular melanoma. Genome Biol. 22:852021. View Article : Google Scholar : PubMed/NCBI | |
|
Huang Y, Luo G, Peng K, Song Y, Wang Y, Zhang H, Li J, Qiu X, Pu M, Liu X, et al: Lactylation stabilizes TFEB to elevate autophagy and lysosomal activity. J Cell Biol. 223:e2023080992024. View Article : Google Scholar : PubMed/NCBI | |
|
Yang Z, Yan C, Ma J, Peng P, Ren X, Cai S, Shen X, Wu Y, Zhang S, Wang X, et al: Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma. Nat Metab. 5:61–79. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Yang J, Luo L, Zhao C, Li X, Wang Z, Zeng Z, Yang X, Zheng X, Jie H, Kang L, et al: A positive feedback loop between inactive VHL-triggered histone lactylation and PDGFRβ signaling drives clear cell renal cell carcinoma progression. Int J Biol Sci. 18:3470–3483. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Hou X, Ouyang J, Tang L, Wu P, Deng X, Yan Q, Shi L, Fan S, Fan C, Guo C, et al: KCNK1 promotes proliferation and metastasis of breast cancer cells by activating lactate dehydrogenase A (LDHA) and up-regulating H3K18 lactylation. PLoS Biol. 22:e30026662024. View Article : Google Scholar : PubMed/NCBI | |
|
Sun L, Zhang Y, Yang B, Sun S, Zhang P, Luo Z, Feng T, Cui Z, Zhu T, Li Y, et al: Lactylation of METTL16 promotes cuproptosis via m6A-modification on FDX1 mRNA in gastric cancer. Nat Commun. 14:65232023. View Article : Google Scholar : PubMed/NCBI | |
|
Xie B, Lin J, Chen X, Zhou X, Zhang Y, Fan M, Xiang J, He N, Hu Z and Wang F: CircXRN2 suppresses tumor progression driven by histone lactylation through activating the Hippo pathway in human bladder cancer. Mol Cancer. 22:1512023. View Article : Google Scholar : PubMed/NCBI | |
|
Wang X, Ying T, Yuan J, Wang Y, Su X, Chen S, Zhao Y, Zhao Y, Sheng J, Teng L, et al: BRAFV600E restructures cellular lactylation to promote anaplastic thyroid cancer proliferation. Endocr Relat Cancer. 30:e2203442023. View Article : Google Scholar : PubMed/NCBI | |
|
Dai E, Wang W and Li Y, Ye D and Li Y: Lactate and lactylation: Behind the development of tumors. Cancer Lett. 591:2168962024. View Article : Google Scholar : PubMed/NCBI | |
|
Li F, Si W, Xia L, Yin D, Wei T, Tao M, Cui X, Yang J, Hong T and Wei R: Positive feedback regulation between glycolysis and histone lactylation drives oncogenesis in pancreatic ductal adenocarcinoma. Mol Cancer. 23:902024. View Article : Google Scholar : PubMed/NCBI | |
|
Jing F, Zhang J, Zhang H and Li T: Unlocking the multifaceted molecular functions and diverse disease implications of lactylation. Biol Rev Camb Philos Soc. 100:172–189. 2025. View Article : Google Scholar : PubMed/NCBI | |
|
Xia Y, Sun M, Huang H and Jin WL: Drug repurposing for cancer therapy. Signal Transduct Target Ther. 9:922024. View Article : Google Scholar : PubMed/NCBI | |
|
Chen H, Li Y, Li H, Chen X, Fu H, Mao D, Chen W, Lan L, Wang C, Hu K, et al: NBS1 lactylation is required for efficient DNA repair and chemotherapy resistance. Nature. 631:663–669. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Chen Y, Wu J, Zhai L, Zhang T, Yin H, Gao H, Zhao F, Wang Z, Yang X, Jin M, et al: Metabolic regulation of homologous recombination repair by MRE11 lactylation. Cell. 187:294–311.e21. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Li G, Wang D, Zhai Y, Pan C, Zhang J, Wang C, Huang R, Yu M, Li Y, Liu X, et al: Glycometabolic reprogramming-induced XRCC1 lactylation confers therapeutic resistance in ALDH1A3-overexpressing glioblastoma. Cell Metab. 36:1696–1710.e10. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Yue Q, Wang Z, Shen Y, Lan Y, Zhong X, Luo X, Yang T, Zhang M, Zuo B, Zeng T, et al: Histone H3K9 lactylation confers temozolomide resistance in glioblastoma via LUC7L2-mediated MLH1 intron retention. Adv Sci (Weinh). 11:e23092902024. View Article : Google Scholar : PubMed/NCBI | |
|
Li F, Zhang H, Huang Y, Li D, Zheng Z, Xie K, Cao C, Wang Q, Zhao X, Huang Z, et al: Single-cell transcriptome analysis reveals the association between histone lactylation and cisplatin resistance in bladder cancer. Drug Resist Updat. 73:1010592024. View Article : Google Scholar : PubMed/NCBI | |
|
Li W, Zhou C, Yu L, Hou Z, Liu H, Kong L, Xu Y, He J, Lan J, Ou Q, et al: Tumor-derived lactate promotes resistance to bevacizumab treatment by facilitating autophagy enhancer protein RUBCNL expression through histone H3 lysine 18 lactylation (H3K18la) in colorectal cancer. Autophagy. 20:114–130. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Komedchikova EN, Kolesnikova OA, Syuy AV, Volkov VS, Deyev SM, Nikitin MP and Shipunova VO: Targosomes: Anti-HER2 PLGA nanocarriers for bioimaging, chemotherapy and local photothermal treatment of tumors and remote metastases. J Control Release. 365:317–330. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Chen S, Xu Y, Zhuo W and Zhang L: The emerging role of lactate in tumor microenvironment and its clinical relevance. Cancer Lett. 590:2168372024. View Article : Google Scholar : PubMed/NCBI | |
|
Wang S, Qi X, Liu D, Xie D, Jiang B, Wang J, Wang X and Wu G: The implications for urological malignancies of non-coding RNAs in the the tumor microenvironment. Comput Struct Biotechnol J. 23:491–505. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Li Y, Cao Q, Hu Y, He B, Cao T, Tang Y, Zhou XP, Lan XP and Liu SQ: Advances in the interaction of glycolytic reprogramming with lactylation. Biomed Pharmacother. 177:1169822024. View Article : Google Scholar : PubMed/NCBI | |
|
Li X, Yang Y, Zhang B, Lin X, Fu X, An Y, Zou Y, Wang JX, Wang Z and Yu T: Lactate metabolism in human health and disease. Signal Transduct Target Ther. 7:3052022. View Article : Google Scholar : PubMed/NCBI | |
|
Wang JX, Choi SYC, Niu X, Kang N, Xue H, Killam J and Wang Y: Lactic acid and an acidic tumor microenvironment suppress anticancer immunity. Int J Mol Sci. 21:83632020. View Article : Google Scholar : PubMed/NCBI | |
|
Huber V, Camisaschi C, Berzi A, Ferro S, Lugini L, Triulzi T, Tuccitto A, Tagliabue E, Castelli C and Rivoltini L: Cancer acidity: An ultimate frontier of tumor immune escape and a novel target of immunomodulation. Semin Cancer Biol. 43:74–89. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Qu J, Li P and Sun Z: Histone lactylation regulates cancer progression by reshaping the tumor microenvironment. Front Immunol. 14:12843442023. View Article : Google Scholar : PubMed/NCBI | |
|
Xiong J, He J, Zhu J, Pan J, Liao W, Ye H, Wang H, Song Y, Du Y, Cui B, et al: Lactylation-driven METTL3-mediated RNA m6A modification promotes immunosuppression of tumor-infiltrating myeloid cells. Mol Cell. 82:1660–1677.e10. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Gu J, Zhou J, Chen Q, Xu X, Gao J, Li X, Shao Q, Zhou B, Zhou H, Wei S, et al: Tumor metabolite lactate promotes tumorigenesis by modulating MOESIN lactylation and enhancing TGF-β signaling in regulatory T cells. Cell Rep. 40:1111222022. View Article : Google Scholar : PubMed/NCBI | |
|
Chevrier S, Levine JH, Zanotelli VRT, Silina K, Schulz D, Bacac M, Ries CH, Ailles L, Jewett MAS, Moch H, et al: An immune atlas of clear cell renal cell carcinoma. Cell. 169:736–749.e18. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Cai J, Song L, Zhang F, Wu S, Zhu G, Zhang P, Chen S, Du J, Wang B, Cai Y, et al: Targeting SRSF10 might inhibit M2 macrophage polarization and potentiate anti-PD-1 therapy in hepatocellular carcinoma. Cancer Commun (Lond). 44:1231–1260. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Chaudagar K, Hieromnimon HM, Khurana R, Labadie B, Hirz T, Mei S, Hasan R, Shafran J, Kelley A, Apostolov E, et al: Reversal of lactate and PD-1-mediated macrophage immunosuppression controls growth of PTEN/p53-deficient prostate cancer. Clin Cancer Res. 29:1952–1968. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Sun L, Zhang H and Gao P: Metabolic reprogramming and epigenetic modifications on the path to cancer. Protein Cell. 13:877–919. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Jiang SS, Kang ZR, Chen YX and Fang JY: The gut microbiome modulate response to immunotherapy in cancer. Sci China Life Sci. 68:381–396. 2025. View Article : Google Scholar : PubMed/NCBI | |
|
Xie Y, Xie F, Zhou X, Zhang L, Yang B, Huang J, Wang F, Yan H, Zeng L, Zhang L and Zhou F: Microbiota in tumors: From understanding to application. Adv Sci (Weinh). 9:e22004702022. View Article : Google Scholar : PubMed/NCBI | |
|
Sepich-Poore GD, Zitvogel L, Straussman R, Hasty J, Wargo JA and Knight R: The microbiome and human cancer. Science. 371:eabc45522021. View Article : Google Scholar : PubMed/NCBI | |
|
Mischke M and Plösch T: The gut microbiota and their metabolites: Potential implications for the host epigenome. Adv Exp Med Biol. 902:33–44. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Woo V and Alenghat T: Epigenetic regulation by gut microbiota. Gut Microbes. 14:20224072022. View Article : Google Scholar : PubMed/NCBI | |
|
Shock T, Badang L, Ferguson B and Martinez-Guryn K: The interplay between diet, gut microbes, and host epigenetics in health and disease. J Nutr Biochem. 95:1086312021. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang Z, Chen Y, Zheng Y, Wang L, Shen S, Yang G, Yang Y and Wang T: Quxie capsule alleviates colitis-associated colorectal cancer through modulating the gut microbiota and suppressing A. fumigatus-induced aerobic glycolysis. Integr Cancer Ther. 21:153473542211385342022. View Article : Google Scholar : PubMed/NCBI | |
|
Sun S, Xu X, Liang L, Wang X, Bai X, Zhu L, He Q, Liang H, Xin X, Wang L, et al: Lactic acid-producing probiotic saccharomyces cerevisiae attenuates ulcerative colitis via suppressing macrophage pyroptosis and modulating gut microbiota. Front Immunol. 12:7776652021. View Article : Google Scholar : PubMed/NCBI | |
|
Wang J, Liu Z, Xu Y, Wang Y, Wang F, Zhang Q, Ni C, Zhen Y, Xu R, Liu Q, et al: Enterobacterial LPS-inducible LINC00152 is regulated by histone lactylation and promotes cancer cells invasion and migration. Front Cell Infect Microbiol. 12:9138152022. View Article : Google Scholar : PubMed/NCBI | |
|
Wang SP, Rubio LA, Duncan SH, Donachie GE, Holtrop G, Lo G, Farquharson FM, Wagner J, Parkhill J, Louis P, et al: Pivotal roles for pH, lactate, and lactate-utilizing bacteria in the stability of a human colonic microbial ecosystem. mSystems. 5:e00645–20. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Koh A, De Vadder F, Kovatcheva-Datchary P and Bäckhed F: From dietary fiber to host physiology: Short-chain fatty acids as key bacterial metabolites. Cell. 165:1332–1345. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Li Z, Gong T, Wu Q, Zhang Y, Zheng X, Li Y, Ren B, Peng X and Zhou X: Lysine lactylation regulates metabolic pathways and biofilm formation in streptococcus mutans. Sci Signal. 16:eadg18492023. View Article : Google Scholar : PubMed/NCBI | |
|
Wang Y, Liu Y, Xiang G, Jian Y, Yang Z, Chen T, Ma X, Zhao N, Dai Y, Lv Y, et al: Post-translational toxin modification by lactate controls staphylococcus aureus virulence. Nat Commun. 15:98352024. View Article : Google Scholar : PubMed/NCBI | |
|
Lin J, Liu G, Chen L, Kwok HF and Lin Y: Targeting lactate-related cell cycle activities for cancer therapy. Semin Cancer Biol. 86:1231–1243. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Fan H, Yang F, Xiao Z, Luo H, Chen H, Chen Z, Liu Q and Xiao Y: Lactylation: Novel epigenetic regulatory and therapeutic opportunities. Am J Physiol Endocrinol Metab. 324:E330–E338. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang Q, Cao L and Xu K: Role and mechanism of lactylation in cancer. Zhongguo Fei Ai Za Zhi. 27:471–479. 2024.(In Chinese). PubMed/NCBI | |
|
De Cesare M, Pratesi G, Giusti A, Polizzi D and Zunino F: Stimulation of the apoptotic response as a basis for the therapeutic synergism of lonidamine and cisplatin in combination in human tumour xenografts. Br J Cancer. 77:434–439. 1998. View Article : Google Scholar : PubMed/NCBI | |
|
Shu Y, Yue J, Li Y, Yin Y, Wang J, Li T, He X, Liang S, Zhang G, Liu Z and Wang Y: Development of human lactate dehydrogenase a inhibitors: High-throughput screening, molecular dynamics simulation and enzyme activity assay. J Comput Aided Mol Des. 38:282024. View Article : Google Scholar : PubMed/NCBI | |
|
Pan L, Feng F, Wu J, Fan S, Han J, Wang S, Yang L, Liu W, Wang C and Xu K: Demethylzeylasteral targets lactate by inhibiting histone lactylation to suppress the tumorigenicity of liver cancer stem cells. Pharmacol Res. 181:1062702022. View Article : Google Scholar : PubMed/NCBI | |
|
Su J, Zheng Z, Bian C, Chang S, Bao J, Yu H, Xin Y and Jiang X: Functions and mechanisms of lactylation in carcinogenesis and immunosuppression. Front Immunol. 14:12530642023. View Article : Google Scholar : PubMed/NCBI | |
|
Smith LE and Rogowska-Wrzesinska A: The challenge of detecting modifications on proteins. Essays Biochem. 64:135–153. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Hao Y, Gu C, Luo W, Shen J, Xie F, Zhao Y, Song X, Han Z and He J: The role of protein post-translational modifications in prostate cancer. PeerJ. 12:e177682024. View Article : Google Scholar : PubMed/NCBI | |
|
Xin Q, Wang H, Li Q, Liu S, Qu K, Liu C and Zhang J: Lactylation: A passing fad or the future of posttranslational modification. Inflammation. 45:1419–1429. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Gao X, Pang C, Fan Z, Wang Y, Duan Y and Zhan H: Regulation of newly identified lysine lactylation in cancer. Cancer Lett. 587:2166802024. View Article : Google Scholar : PubMed/NCBI | |
|
Vétizou M, Pitt JM, Daillère R, Lepage P, Waldschmitt N, Flament C, Rusakiewicz S, Routy B, Roberti MP, Duong CPM, et al: Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 350:1079–1084. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Gori S, Inno A, Belluomini L, Bocus P, Bisoffi Z, Russo A and Arcaro G: Gut microbiota and cancer: How gut microbiota modulates activity, efficacy and toxicity of antitumoral therapy. Crit Rev Oncol Hematol. 143:139–147. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Wu Z, Huang R and Yuan L: Crosstalk of intracellular post-translational modifications in cancer. Arch Biochem Biophys. 676:1081382019. View Article : Google Scholar : PubMed/NCBI | |
|
Tomasi ML and Ramani K: SUMOylation and phosphorylation cross-talk in hepatocellular carcinoma. Transl Gastroenterol Hepatol. 3:202018. View Article : Google Scholar : PubMed/NCBI |
