Importance of the Keap1-Nrf2 pathway in NSCLC: Is it a possible biomarker? (Review)
- Authors:
- Raúl Barrera-Rodríguez
-
Affiliations: Department of Biochemistry and Environmental Medicine, National Institute of Respiratory Diseases, Mexico City 14080, Mexico - Published online on: September 5, 2018 https://doi.org/10.3892/br.2018.1143
- Pages: 375-382
This article is mentioned in:
Abstract
Siegel RL, Miller KD and Jemal A: Cancer Statistics, 2017. CA Cancer J Clin. 67:7–30. 2017. View Article : Google Scholar : PubMed/NCBI | |
Cheng TY, Cramb SM, Baade PD, Youlden DR, Nwogu C and Reid ME: The international epidemiology of lung cancer: Latest trends, disparities, and tumor characteristics. J Thorac Oncol. 11:1653–1671. 2016. View Article : Google Scholar : PubMed/NCBI | |
Forde PM and Ettinger DS: Targeted therapy for non-small-cell lung cancer: Past, present and future. Expert Rev Anticancer Ther. 13:745–758. 2013. View Article : Google Scholar : PubMed/NCBI | |
Novello S, Barlesi F, Califano R, Cufer T, Ekman S, Levra MG, Kerr K, Popat S, Reck M, Senan S, et al: ESMO Guidelines Committee: Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 27 Suppl 5:v1–v27. 2016. View Article : Google Scholar : PubMed/NCBI | |
Kim ES: Chemotherapy Resistance in Lung Cancer. Adv Exp Med Biol. 893:189–209. 2016. View Article : Google Scholar : PubMed/NCBI | |
Rahman I, Biswas SK and Kode A: Oxidant and antioxidant balance in the airways and airway diseases. Eur J Pharmacol. 533:222–239. 2006. View Article : Google Scholar : PubMed/NCBI | |
Zhang JY, Wang Y and Prakash C: Xenobiotic-metabolizing enzymes in human lung. Curr Drug Metab. 7:939–948. 2006. View Article : Google Scholar : PubMed/NCBI | |
Jaramillo MC and Zhang DD: The emerging role of the Nrf2-Keap1 signaling pathway in cancer. Genes Dev. 27:2179–2191. 2013. View Article : Google Scholar : PubMed/NCBI | |
Ma Q: Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol. 53:401–426. 2013. View Article : Google Scholar : PubMed/NCBI | |
Singh A, Misra V, Thimmulappa RK, Lee H, Ames S, Hoque MO, Herman JG, Baylin SB, Sidransky D, Gabrielson E, et al: Dysfunctional KEAP1-NRF2 interaction in non-small-cell lung cancer. PLoS Med. 3:e4202006. View Article : Google Scholar : PubMed/NCBI | |
Ohta T, Iijima K, Miyamoto M, Nakahara I, Tanaka H, Ohtsuji M, Suzuki T, Kobayashi A, Yokota J, Sakiyama T, et al: Loss of Keap1 function activates Nrf2 and provides advantages for lung cancer cell growth. Cancer Res. 68:1303–1309. 2008. View Article : Google Scholar : PubMed/NCBI | |
Wang R, An J, Ji F, Jiao H, Sun H and Zhou D: Hypermethylation of the Keap1 gene in human lung cancer cell lines and lung cancer tissues. Biochem Biophys Res Commun. 373:151–154. 2008. View Article : Google Scholar : PubMed/NCBI | |
Vollrath V, Wielandt AM, Iruretagoyena M and Chianale J: Role of Nrf2 in the regulation of the Mrp2 (ABCC2) gene. Biochem J. 395:599–609. 2006. View Article : Google Scholar : PubMed/NCBI | |
Lu MC, Ji JA, Jiang ZY and You QD: The Keap1-Nrf2-ARE pathway as a potential preventive and therapeutic target: An update. Med Res Rev. 36:924–963. 2016. View Article : Google Scholar : PubMed/NCBI | |
Sporn MB and Liby KT: NRF2 and cancer: The good, the bad and the importance of context. Nat Rev Cancer. 12:564–571. 2012. View Article : Google Scholar : PubMed/NCBI | |
Villeneuve NF, Lau A and Zhang DD: Regulation of the Nrf2-Keap1 antioxidant response by the ubiquitin proteasome system: An insight into cullin-ring ubiquitin ligases. Antioxid Redox Signal. 13:1699–1712. 2010. View Article : Google Scholar : PubMed/NCBI | |
Menegon S, Columbano A and Giordano S: The dual roles of NRF2 in cancer. Trends Mol Med. 22:578–593. 2016. View Article : Google Scholar : PubMed/NCBI | |
Kobayashi A, Kang MI, Okawa H, Ohtsuji M, Zenke Y, Chiba T, Igarashi K and Yamamoto M: Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2. Mol Cell Biol. 24:7130–7139. 2004. View Article : Google Scholar : PubMed/NCBI | |
Theodore M, Kawai Y, Yang J, Kleshchenko Y, Reddy SP, Villalta F and Arinze IJ: Multiple nuclear localization signals function in the nuclear import of the transcription factor Nrf2. J Biol Chem. 283:8984–8994. 2008. View Article : Google Scholar : PubMed/NCBI | |
Padmanabhan B, Tong KI, Ohta T, Nakamura Y, Scharlock M, Ohtsuji M, Kang MI, Kobayashi A, Yokoyama S and Yamamoto M: Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer. Mol Cell. 21:689–700. 2006. View Article : Google Scholar : PubMed/NCBI | |
Kim YR, Oh JE, Kim MS, Kang MR, Park SW, Han JY, Eom HS, Yoo NJ and Lee SH: Oncogenic NRF2 mutations in squamous cell carcinomas of oesophagus and skin. J Pathol. 220:446–451. 2010. View Article : Google Scholar : PubMed/NCBI | |
Nioi P and Nguyen T: A mutation of Keap1 found in breast cancer impairs its ability to repress Nrf2 activity. Biochem Biophys Res Commun. 362:816–821. 2007. View Article : Google Scholar : PubMed/NCBI | |
Taguchi K and Yamamoto M: The KEAP1-NRF2 system in cancer. Front Oncol. 7:852017. View Article : Google Scholar : PubMed/NCBI | |
Muscarella LA, Parrella P, D'Alessandro V, la Torre A, Barbano R, Fontana A, Tancredi A, Guarnieri V, Balsamo T, Coco M, et al: Frequent epigenetics inactivation of KEAP1 gene in non-small cell lung cancer. Epigenetics. 6:710–719. 2011. View Article : Google Scholar : PubMed/NCBI | |
Khor TO, Fuentes F, Shu L, Paredes-Gonzalez X, Yang AY, Liu Y, Smiraglia DJ, Yegnasubramanian S, Nelson WG and Kong AN: Epigenetic DNA methylation of antioxidative stress regulator NRF2 in human prostate cancer. Cancer Prev Res (Phila). 7:1186–1197. 2014. View Article : Google Scholar : PubMed/NCBI | |
Guo Y, Yu S, Zhang C and Kong AN: Epigenetic regulation of Keap1-Nrf2 signaling. Free Radic Biol Med. 88:337–349. 2015. View Article : Google Scholar : PubMed/NCBI | |
Chen W, Sun Z, Wang XJ, Jiang T, Huang Z, Fang D and Zhang DD: Direct interaction between Nrf2 and p21(Cip1/WAF1) upregulates the Nrf2-mediated antioxidant response. Mol Cell. 34:663–673. 2009. View Article : Google Scholar : PubMed/NCBI | |
Williams AB and Schumacher B: p53 in the DNA-damage-repair process. Cold Spring Harb Perspect Med. 6:a0260702016. View Article : Google Scholar : PubMed/NCBI | |
Komatsu M, Kurokawa H, Waguri S, Taguchi K, Kobayashi A, Ichimura Y, Sou YS, Ueno I, Sakamoto A, Tong KI, et al: The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1. Nat Cell Biol. 12:213–223. 2010. View Article : Google Scholar : PubMed/NCBI | |
Faraonio R, Vergara P, Di Marzo D, Pierantoni MG, Napolitano M, Russo T and Cimino F: p53 suppresses the Nrf2-dependent transcription of antioxidant response genes. J Biol Chem. 281:39776–39784. 2006. View Article : Google Scholar : PubMed/NCBI | |
Ichimura Y, Waguri S, Sou YS, Kageyama S, Hasegawa J, Ishimura R, Saito T, Yang Y, Kouno T, Fukutomi T, et al: Phosphorylation of p62 activates the Keap1-Nrf2 pathway during selective autophagy. Mol Cell. 51:618–631. 2013. View Article : Google Scholar : PubMed/NCBI | |
Taguchi K, Fujikawa N, Komatsu M, Ishii T, Unno M, Akaike T, Motohashi H and Yamamoto M: Keap1 degradation by autophagy for the maintenance of redox homeostasis. Proc Natl Acad Sci USA. 109:13561–13566. 2012. View Article : Google Scholar : PubMed/NCBI | |
DeNicola GM, Karreth FA, Humpton TJ, Gopinathan A, Wei C, Frese K, Mangal D, Yu KH, Yeo CJ, Calhoun ES, et al: Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature. 475:106–109. 2011. View Article : Google Scholar : PubMed/NCBI | |
Kinch L, Grishin NV and Brugarolas J: Succination of Keap1 and activation of Nrf2-dependent antioxidant pathways in FH-deficient papillary renal cell carcinoma type 2. Cancer Cell. 20:418–420. 2011. View Article : Google Scholar : PubMed/NCBI | |
Adam J, Hatipoglu E, O'Flaherty L, Ternette N, Sahgal N, Lockstone H, Baban D, Nye E, Stamp GW, Wolhuter K, et al: Renal cyst formation in Fh1-deficient mice is independent of the Hif/Phd pathway: Roles for fumarate in KEAP1 succination and Nrf2 signaling. Cancer Cell. 20:524–537. 2011. View Article : Google Scholar : PubMed/NCBI | |
DeNicola GM, Chen PH, Mullarky E, Sudderth JA, Hu Z, Wu D, Tang H, Xie Y, Asara JM, Huffman KE, et al: NRF2 regulates serine biosynthesis in non-small cell lung cancer. Nat Genet. 47:1475–1481. 2015. View Article : Google Scholar : PubMed/NCBI | |
Mitsuishi Y, Taguchi K, Kawatani Y, Shibata T, Nukiwa T, Aburatani H, Yamamoto M and Motohashi H: Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming. Cancer Cell. 22:66–79. 2012. View Article : Google Scholar : PubMed/NCBI | |
Goldstein LD, Lee J, Gnad F, Klijn C, Schaub A, Reeder J, Daemen A, Bakalarski CE, Holcomb T, Shames DS, et al: Recurrent loss of NFE2L2 Exon 2 is a mechanism for Nrf2 pathway activation in human cancers. Cell Rep. 16:2605–2617. 2016. View Article : Google Scholar : PubMed/NCBI | |
Shibata T, Ohta T, Tong KI, Kokubu A, Odogawa R, Tsuta K, Asamura H, Yamamoto M and Hirohashi S: Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy. Proc Natl Acad Sci USA. 105:13568–13573. 2008. View Article : Google Scholar : PubMed/NCBI | |
Chowdhry S, Zhang Y, McMahon M, Sutherland C, Cuadrado A and Hayes JD: Nrf2 is controlled by two distinct β-TrCP recognition motifs in its Neh6 domain, one of which can be modulated by GSK-3 activity. Oncogene. 32:3765–3781. 2013. View Article : Google Scholar : PubMed/NCBI | |
Koundouros N and Poulogiannis G: Phosphoinositide 3-kinase/Akt signaling and redox metabolism in cancer. Front Oncol. 8:1602018. View Article : Google Scholar : PubMed/NCBI | |
Inoue D, Suzuki T, Mitsuishi Y, Miki Y, Suzuki S, Sugawara S, Watanabe M, Sakurada A, Endo C, Uruno A, et al: Accumulation of p62/SQSTM1 is associated with poor prognosis in patients with lung adenocarcinoma. Cancer Sci. 103:760–766. 2012. View Article : Google Scholar : PubMed/NCBI | |
Yang H, Wang W, Zhang Y, Zhao J, Lin E, Gao J and He J: The role of NF-E2-related factor 2 in predicting chemoresistance and prognosis in advanced non-small-cell lung cancer. Clin Lung Cancer. 12:166–171. 2011. View Article : Google Scholar : PubMed/NCBI | |
Solis LM, Behrens C, Dong W, Suraokar M, Ozburn NC, Moran CA, Corvalan AH, Biswal S, Swisher SG, Bekele BN, et al: Nrf2 and Keap1 abnormalities in non-small cell lung carcinoma and association with clinicopathologic features. Clin Cancer Res. 16:3743–3753. 2010. View Article : Google Scholar : PubMed/NCBI | |
Li QK, Singh A, Biswal S, Askin F and Gabrielson E: KEAP1 gene mutations and NRF2 activation are common in pulmonary papillary adenocarcinoma. J Hum Genet. 56:230–234. 2011. View Article : Google Scholar : PubMed/NCBI | |
Kim Y, Hammerman PS, Kim J, Yoon JA, Lee Y, Sun JM, Wilkerson MD, Pedamallu CS, Cibulskis K, Yoo YK, et al: Integrative and comparative genomic analysis of lung squamous cell carcinomas in East Asian patients. J Clin Oncol. 32:121–128. 2014. View Article : Google Scholar : PubMed/NCBI | |
Frank R, Scheffler M, Merkelbach-Bruse S, Ihle MA, Kron A, Rauer M, Ueckeroth F, König K, Michels S, Fischer R, et al: Clinical and pathological characteristics of KEAP1- and NFE2L2-mutated non-small cell lung carcinoma (NSCLC). Clin Cancer Res. 24:3087–3096. 2018. View Article : Google Scholar : PubMed/NCBI | |
Campbell JD, Alexandrov A, Kim J, Wala J, Berger AH, Pedamallu CS, Shukla SA, Guo G, Brooks AN, Murray BA, et al: Cancer Genome Atlas Research Network: Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas. Nat Genet. 48:607–616. 2016. View Article : Google Scholar : PubMed/NCBI | |
Hayes JD and McMahon M: NRF2 and KEAP1 mutations: Permanent activation of an adaptive response in cancer. Trends Biochem Sci. 34:176–188. 2009. View Article : Google Scholar : PubMed/NCBI | |
Cancer Genome Atlas Research Network: Comprehensive genomic characterization of squamous cell lung cancers. Nature. 489:519–525. 2012. View Article : Google Scholar : PubMed/NCBI | |
Riely GJ, Jordan E, Kim HR, Yu HA, Berger MF and Solit DB: Association of outcomes and co-occurring genomic alterations in patients with KRAS-mutant non-small cell lung cancer. J Clin Oncol. 34:90192016. View Article : Google Scholar | |
Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, Lee W, Yuan J, Wong P, Ho TS, et al: Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 348:124–128. 2015. View Article : Google Scholar : PubMed/NCBI | |
Scheel AH, Ansén S, Schultheis AM, Scheffler M, Fischer RN, Michels S, Hellmich M, George J, Zander T, Brockmann M, et al: PD-L1 expression in non-small cell lung cancer: Correlations with genetic alterations. Oncoimmunology. 5:e11313792016. View Article : Google Scholar : PubMed/NCBI | |
Bethune G, Bethune D, Ridgway N and Xu Z: Epidermal growth factor receptor (EGFR) in lung cancer: An overview and update. J Thorac Dis. 2:48–51. 2010.PubMed/NCBI | |
Seshacharyulu P, Ponnusamy MP, Haridas D, Jain M, Ganti AK and Batra SK: Targeting the EGFR signaling pathway in cancer therapy. Expert Opin Ther Targets. 16:15–31. 2012. View Article : Google Scholar : PubMed/NCBI | |
Kobayashi S, Boggon TJ, Dayaram T, Jänne PA, Kocher O, Meyerson M, Johnson BE, Eck MJ, Tenen DG and Halmos B: EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med. 352:786–792. 2005. View Article : Google Scholar : PubMed/NCBI | |
Papaiahgari S, Yerrapureddy A, Hassoun PM, Garcia JG, Birukov KG and Reddy SP: EGFR-activated signaling and actin remodeling regulate cyclic stretch-induced NRF2-ARE activation. Am J Respir Cell Mol Biol. 36:304–312. 2007. View Article : Google Scholar : PubMed/NCBI | |
Jacobsen K, Bertran-Alamillo J, Molina MA, Teixidó C, Karachaliou N, Pedersen MH, Castellví J, Garzón M, Codony-Servat C, Codony-Servat J, et al: Convergent Akt activation drives acquired EGFR inhibitor resistance in lung cancer. Nat Commun. 8:4102017. View Article : Google Scholar : PubMed/NCBI | |
Huo L, Li CW, Huang TH, Lam YC, Xia W, Tu C, Chang WC, Hsu JL, Lee DF, Nie L, et al: Activation of Keap1/Nrf2 signaling pathway by nuclear epidermal growth factor receptor in cancer cells. Am J Transl Res. 6:649–663. 2014.PubMed/NCBI | |
Denduluri SK, Idowu O, Wang Z, Liao Z, Yan Z, Mohammed MK, Ye J, Wei Q, Wang J, Zhao L, et al: Insulin-like growth factor (IGF) signaling in tumorigenesis and the development of cancer drug resistance. Genes Dis. 2:13–25. 2015. View Article : Google Scholar : PubMed/NCBI | |
Sasaki H, Hikosaka Y, Okuda K, Kawano O, Moriyama S, Yano M and Fujii Y: NFE2L2 gene mutation in male Japanese squamous cell carcinoma of the lung. J Thorac Oncol. 5:786–789. 2010. View Article : Google Scholar : PubMed/NCBI | |
Takahashi T, Sonobe M, Menju T, Nakayama E, Mino N, Iwakiri S, Nagai S, Sato K, Miyahara R, Okubo K, et al: Mutations in Keap1 are a potential prognostic factor in resected non-small cell lung cancer. J Surg Oncol. 101:500–506. 2010.PubMed/NCBI | |
Ishikawa T, Bao JJ, Yamane Y, Akimaru K, Frindrich K, Wright CD and Kuo MT: Coordinated induction of MRP/GS-X pump and gamma-glutamylcysteine synthetase by heavy metals in human leukemia cells. J Biol Chem. 271:14981–14988. 1996. View Article : Google Scholar : PubMed/NCBI | |
Adachi T, Nakagawa H, Chung I, Hagiya Y, Hoshijima K, Noguchi N, Kuo MT and Ishikawa T: Nrf2-dependent and -independent induction of ABC transporters ABCC1, ABCC2, and ABCG2 in HepG2 cells under oxidative stress. J Exp Ther Oncol. 6:335–348. 2007.PubMed/NCBI | |
Singh A, Wu H, Zhang P, Happel C, Ma J and Biswal S: Expression of ABCG2 (BCRP) is regulated by Nrf2 in cancer cells that confers side population and chemoresistance phenotype. Mol Cancer Ther. 9:2365–2376. 2010. View Article : Google Scholar : PubMed/NCBI | |
Saito H, Hirano H, Nakagawa H, Fukami T, Oosumi K, Murakami K, Kimura H, Kouchi T, Konomi M, Tao E, et al: A new strategy of high-speed screening and quantitative structure-activity relationship analysis to evaluate human ATP-binding cassette transporter ABCG2-drug interactions. J Pharmacol Exp Ther. 317:1114–1124. 2006. View Article : Google Scholar : PubMed/NCBI | |
zu Schwabedissen Meyer HE, Grube M, Dreisbach A, Jedlitschky G, Meissner K, Linnemann K, Fusch C, Ritter CA, Völker U and Kroemer HK: Epidermal growth factor-mediated activation of the map kinase cascade results in altered expression and function of ABCG2 (BCRP). Drug Metab Dispos. 34:524–533. 2006. View Article : Google Scholar : PubMed/NCBI | |
Hayes JD, McMahon M, Chowdhry S and Dinkova-Kostova AT: Cancer chemoprevention mechanisms mediated through the Keap1-Nrf2 pathway. Antioxid Redox Signal. 13:1713–1748. 2010. View Article : Google Scholar : PubMed/NCBI | |
Zhang P, Singh A, Yegnasubramanian S, Esopi D, Kombairaju P, Bodas M, Wu H, Bova SG and Biswal S: Loss of Kelch-like ECH-associated protein 1 function in prostate cancer cells causes chemoresistance and radioresistance and promotes tumor growth. Mol Cancer Ther. 9:336–346. 2010. View Article : Google Scholar : PubMed/NCBI | |
Singh A, Boldin-Adamsky S, Thimmulappa RK, Rath SK, Ashush H, Coulter J, Blackford A, Goodman SN, Bunz F, Watson WH, et al: RNAi-mediated silencing of nuclear factor erythroid-2-related factor 2 gene expression in non-small cell lung cancer inhibits tumor growth and increases efficacy of chemotherapy. Cancer Res. 68:7975–7984. 2008. View Article : Google Scholar : PubMed/NCBI | |
Tian Y, Liu Q, He X, Yuan X, Chen Y, Chu Q and Wu K: Emerging roles of Nrf2 signal in non-small cell lung cancer. J Hematol Oncol. 9:142016. View Article : Google Scholar : PubMed/NCBI | |
Qian Z, Zhou T, Gurguis CI, Xu X, Wen Q, Lv J, Fang F, Hecker L, Cress AE, Natarajan V, et al: Nuclear factor, erythroid 2-like 2-associated molecular signature predicts lung cancer survival. Sci Rep. 5:168892015. View Article : Google Scholar : PubMed/NCBI | |
Mahaffey CM, Zhang H, Rinna A, Holland W, Mack PC and Forman HJ: Multidrug-resistant protein-3 gene regulation by the transcription factor Nrf2 in human bronchial epithelial and non-small-cell lung carcinoma. Free Radic Biol Med. 46:1650–1657. 2009. View Article : Google Scholar : PubMed/NCBI | |
Liu X, Sun C, Liu B, Jin X, Li P, Zheng X, Zhao T, Li F and Li Q: Genistein mediates the selective radiosensitizing effect in NSCLC A549 cells via inhibiting methylation of the keap1 gene promoter region. Oncotarget. 7:27267–27279. 2016.PubMed/NCBI | |
Cho JM, Manandhar S, Lee HR, Park HM and Kwak MK: Role of the Nrf2-antioxidant system in cytotoxicity mediated by anticancer cisplatin: Implication to cancer cell resistance. Cancer Lett. 260:96–108. 2008. View Article : Google Scholar : PubMed/NCBI | |
Copple IM, Dinkova-Kostova AT, Kensler TW, Liby KT and Wigley WC: NRF2 as an emerging therapeutic target. Oxid Med Cell Longev. 2017:81654582017. View Article : Google Scholar : PubMed/NCBI | |
Magesh S, Chen Y and Hu L: Small molecule modulators of Keap1-Nrf2-ARE pathway as potential preventive and therapeutic agents. Med Res Rev. 32:687–726. 2012. View Article : Google Scholar : PubMed/NCBI | |
Abed DA, Goldstein M, Albanyan H, Jin H and Hu L: Discovery of direct inhibitors of Keap1-Nrf2 protein-protein interaction as potential therapeutic and preventive agents. Acta Pharm Sin B. 5:285–299. 2015. View Article : Google Scholar : PubMed/NCBI | |
Harder B, Tian W, La Clair JJ, Tan AC, Ooi A, Chapman E and Zhang DD: Brusatol overcomes chemoresistance through inhibition of protein translation. Mol Carcinog. 56:1493–1500. 2017. View Article : Google Scholar : PubMed/NCBI | |
Ren D, Villeneuve NF, Jiang T, Wu T, Lau A, Toppin HA and Zhang DD: Brusatol enhances the efficacy of chemotherapy by inhibiting the Nrf2-mediated defense mechanism. Proc Natl Acad Sci USA. 108:1433–1438. 2011. View Article : Google Scholar : PubMed/NCBI | |
Olayanju A, Copple IM, Bryan HK, Edge GT, Sison RL, Wong MW, Lai ZQ, Lin ZX, Dunn K, Sanderson CM, et al: Brusatol provokes a rapid and transient inhibition of Nrf2 signaling and sensitizes mammalian cells to chemical toxicity-implications for therapeutic targeting of Nrf2. Free Radic Biol Med. 78:202–212. 2015. View Article : Google Scholar : PubMed/NCBI | |
Kitamura H and Motohashi H: NRF2 addiction in cancer cells. Cancer Sci. 109:900–911. 2018. View Article : Google Scholar : PubMed/NCBI |