Modulation of NRF2 signaling pathway by nuclear receptors: Implications for cancer

• Published in: Biochimica et biophysica acta Vol. 1843; no. 9; pp. 1875 - 1885
• Main Authors: Namani, Akhileshwar, Li, Yulong, Wang, Xiu Jun, Tang, Xiuwen
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2014
• Subjects: Animals; Cancer therapy; Carcinogenesis - metabolism; Carcinogenesis - pathology; Humans; KEAP1; Models, Biological; Neh7; Neoplasms - drug therapy; Neoplasms - metabolism; Neoplasms - pathology; NF-E2-Related Factor 2 - antagonists & inhibitors; NF-E2-Related Factor 2 - metabolism; NRF2; Nuclear receptor; Receptors, Cytoplasmic and Nuclear - metabolism; Signal Transduction; Bcl-2; RAR; Nuclear receptor; Neh7; RXRα; DBD; KEAP1; ChIP; TXS; BBN; DPP3; CBP; NRF2; PPAR; SNP; miRNA; 11β-HSD1; GSH; NQO1; Bach1; ERα; GST; GR; β-TrCP; AKR1C; ERRβ; Neh; Bcl-xL; ARE; Dex; Cancer therapy; ROS; SMRT; ATRA
• ISSN: 0167-4889; 0006-3002; 1879-2596
• DOI: 10.1016/j.bbamcr.2014.05.003

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. •KEAP1–NRF2–ARE pathway•Role of NRF2 in cancer chemoprevention and carcinogenesis•Repression of NRF2 by nuclear receptors•Therapeutic perspective of NRF2 inhibition through nuclear receptors