Dual roles of NRF2 in tumor prevention and progression: Possible implications in cancer treatment |
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| Affiliation: | 1. Department of Pharmacology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea;2. Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul 120-749, Republic of Korea;1. Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur 603203, Tamil Nadu, India;2. Department of Bioinformatics, School of Bioengineering, SRM University, Kattankulathur 603203, Tamil Nadu, India;3. SRM Research Institute, SRM University, Kattankulathur 603203, Tamil Nadu, India;4. Department of Radiology, Stanford University Medical Center, Stanford, CA 94304, USA |
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| Abstract: | The cap’n’collar (CNC) family serves as cellular sensors of oxidative and electrophilic stresses and shares structural similarities including basic leucine zipper (bZIP) and CNC domains. They form heterodimers with small MAF proteins to regulate antioxidant and phase II enzymes through antioxidant response element (ARE)-mediated transactivation. Among the CNC family members, NRF2 is required for systemic protection against redox-mediated injury and carcinogenesis. On the other hand, NRF2 is activated by oncogenic pathways, metabolism, and hypoxia. Constitutive NRF2 activation is observed in a variety of human cancers and it is highly correlated with tumor progression and aggressiveness. In this review, we will discuss how NRF2 plays dual roles in cancer prevention and progression depending on the cellular context and environment. Therefore, a better understanding of NRF2 will be necessary to exploit this complex network of balancing antioxidant pathways to inhibit tumor progression. |
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| Keywords: | Oxidative stress NRF2 CNC family Antioxidant response element ARE Small MAF Cancer |
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