Redox Modulating NRF2: A Potential Mediator of Cancer Stem Cell Resistance

Figure 3

Potential roles of NRF2 signaling in CSCs. In CSC-like cell models, NRF2 is activated through multiple molecular mechanisms in a context-dependent manner. The upregulation of competing proteins such as p62 and p21, activation of PERK, or repressed proteasome function were shown to enhance NRF2 activity in these models. Elevated NRF2 levels in CSCs can contribute to the maintenance of low ROS by upregulating multiple antioxidant genes. In addition, NRF2-mediated expression of ABC transporters elicits efflux of anticancer drugs from cancer cells. Overall, activated NRF2 signaling facilitates CSCs survival and stress resistance, and consequently, it can be suggested that CSCs with high NRF2 activity play a crucial role in tumor recurrence and further progression.