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 is found to play a pivotal role in the control of 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. Cancer-related 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, large-scale genomic and transcriptomic studies are required to correlate the clinical outcomes with the activity of the NRF2 expression system. This review is an attempt to give insights into the understanding of the role of NRF2 in cancer.

Sphingosine 1‐phosphate combining with S1PR4 promotes regulatory T cell differentiation related to FAO through Nrf2/PPARα

“…Nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2), known as a transcription factor, is essential for keeping the balance of oxidative stress, regulating metabolism and modulating inflammation 29 . Oxidative stressors or electrophiles dissociates the Nrf2 from Keap‐1, prevents Nrf2 from degrading and increases nuclear accumulation of Nrf2 30 . Previous studies have demonstrated that Nrf2 could directly inhibit the inflammatory cytokines transcription of immune cells and indirectly limit the inflammatory process through modulating HO‐1 expression 31,32 .…”

“…29 Oxidative stressors or electrophiles dissociates the Nrf2 from Keap-1, prevents Nrf2 from degrading and increases nuclear accumulation of Nrf2. 30 Previous studies have demonstrated that Nrf2 could directly inhibit the inflammatory cytokines transcription of immune cells and indirectly limit the inflammatory process through modulating HO-1 expression. 31,32 Nrf2 participate in immune cell differentiation, including macrophage, dendritic cell and some subtypes of T cells.…”