NRF-2 TRANSCRIPTIONALLY UPREGULATES xCT IN BREAST CANCER

Cancer cells adapt to high levels of oxidative stress in order to survive and proliferate, making the transcription factors involved in antioxidant defence regulation targets of interest. The transcription factor NF E2 Related Factor 2 (NRF-2) regulates cellular defence genes including those encoding intracellular redox-balancing proteins such as enzymes involved in glutathione metabolism. Glutathione in particular is an important intracellular antioxidant molecule. NRF-2 binds to the Antioxidant Response Element (ARE) in the promoter of its target genes. Under basal conditions, Kelch-like ECH-associated protein 1 (KEAP1) acts as an inhibitor that targets NRF-2 for ubiquitination