Understanding the Role of NRF2 Signalling in Cancer

Abstract

Nuclear factor erythroid 2 (NFE 2) - related factor 2 (NFE2L2 or NRF2) is one of the transcription factors predominantly related to the expression of antioxidant genes. NRF2 plays a pivotal role in controlling redox potential in several tumor characteristics, including cancer cell metabolism, stem-cell-like characteristics, tumor aggressiveness, invasion, and metastasis. Further, it was recently discovered that the noncanonical pathway of NRF2 activation was involved in carcinogenesis. Cancerrelated changes (e.g., metabolic flexibility) that support cancer progression were found to be redox and NRF2 dependent. The pro or antineoplastic effects of NRF2 are essentially based on the specific molecular characteristics of the type of cancer. Therefore, systematic investigation of NRF2 signaling is necessary to clarify its role in cancer etiology. Understanding the role of NRF2 in triggering gene expressions in different types of cancer is quite challenging, which might be useful to target those genes for better clinical outcomes. To decipher the role of NRF2 in tumor formation and progression, largescale genomic and transcriptomic studies are required to correlate the clinical outcomes with the activity of the NRF2 expression system. This review attempts to give insights into the understanding of the role of NRF2 in cancer.

Keywords: KEAP 1; NRF2; cancer; carcinogenesis; gene expression; redox potential.