NFE2L2 and melanoma: Furthermore, evidence indicates that NRF2 can transcriptionally upregulate CHAC1, as observed in ferroptosis-resistant melanoma cells where CHAC1 induction occurs independently of ER stress (Gagliardi et al., 2019) and modestly at the promoter level (Crawford et al., 2015) The stabilized NRF2 enhances expression of antioxidant defense genes, including the cystine/glutamate antiporter system (xCT) (subunit SLC7A11), which imports cystine for de novo GSH synthesis (Kreß et al., 2023).