Modulation of NRF2 signaling pathway by nuclear receptors: implications for cancer.
Nuclear factor-erythroid 2 p45-related factor 2 (NRF2, also known as Nfe2l2) plays a critical role in regulating cellular defense against electrophilic and oxidative stress by activating the expression of an array of antioxidant response element-dependent genes. On one hand, NRF2 activators have been used in clinical trials for cancer prevention and the treatment of diseases associated with oxidative stress; on the other hand, constitutive activation of NRF2 in many types of tumors contributes to the survival and growth of cancer cells, as well as resistance to anticancer therapy. In this review, we provide an overview of the NRF2 signaling pathway and discuss its role in carcinogenesis. We also introduce the inhibition of NRF2 by nuclear receptors. Further, we address the biological significance of regulation of the NRF2 signaling pathway by nuclear receptors in health and disease. Finally, we discuss the possible impact of NRF2 inhibition by nuclear receptors on cancer therapy.
Department of Biochemistry and Genetics, Zhejiang University School of Medicine, Hangzhou 310058, PR China.
Akhileshwar
A
Namani
Department of Biochemistry and Genetics, Zhejiang University School of Medicine, Hangzhou 310058, PR China.
Yulong
Y
Li
Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou 310058, PR China. Electronic address: xjwang@zju.edu.cn.
Xiu Jun
XJ
Wang
Department of Biochemistry and Genetics, Zhejiang University School of Medicine, Hangzhou 310058, PR China. Electronic address: xiuwentang@zju.edu.cn.
Xiuwen
X
Tang
D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008954:Models, Biological; D051267:NF-E2-Related Factor 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D015398:Signal Transduction
D051267:NF-E2-Related Factor 2; D018160:Receptors, Cytoplasmic and Nuclear
Cancer therapy; KEAP1; NRF2; Neh7; Nuclear receptor