Thiol starvation triggers melanoma state switching in an ATF4 and NRF2-dependent manner.

ABSTRACT: The cystine/glutamate antiporter xCT is an important source of cysteine for cancer cells. Once taken up, cystine is reduced to cysteine and serves as a building block for the synthesis of glutathione, which efficiently protects cells from oxidative damage and prevents ferroptosis. As melanomas are particularly exposed to several sources of oxidative stress, we investigated the biological role of cysteine and glutathione supply by xCT in melanoma. xCT activity was abolished by genetic depletion in the Tyr::CreER; Braf^CA; Pten^lox/+ melanoma model and by acute cystine withdrawal in melanoma cell lines. Both interventions profoundly impacted melanoma glutathione levels, but they were surprisingly well tolerated by murine melanomas in vivo and by most human melanoma cell l

SUBMITTER: Meinert M 

PROVIDER: S-EPMC10825660 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature