Dual roles of NRF2 in tumor prevention and progression: Possible implications in cancer treatment

• Published in: Free radical biology & medicine 2015-02, Vol.79, p.292-299
• Main Authors: Moon, Eui Jung, Giaccia, Amato
• Format: Article
• Language: English
• Subjects: Animals; Antioxidant response element; ARE; Cancer; CNC family; Disease Progression; Genes, Tumor Suppressor; Humans; Hypoxia; Mice; Mice, Knockout; Neoplasms - pathology; Neoplasms - prevention & control; Neoplasms - therapy; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - physiology; NRF2; Oxidative Stress; Signal Transduction; Small MAF
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2014.11.009

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. [Display omitted] •NRF2, a cap’n’collar (CNC) transcription factor, plays dual roles in cancer prevention and progression depending on the cellular context and environment.•Overexpression of NRF2 in many human cancers is significantly involved in tumor metabolism, angiogenesis, and treatment resistance, which results in poor patient survival.•Conflicting roles of NRF2 in cancer prevention and cancer progression remain to be challenged to determine the optimal use of NRF2 activators or inhibitors in the clinic.