SLC7A11 expression level dictates differential responses to oxidative stress in cancer cells.

ABSTRACT: The cystine transporter solute carrier family 7 member 11 (SLC7A11; also called xCT) protects cancer cells from oxidative stress and is overexpressed in many cancers. Here we report a surprising finding that, whereas moderate overexpression of SLC7A11 is beneficial for cancer cells treated with H₂O₂, a common oxidative stress inducer, its high overexpression dramatically increases H₂O₂-induced cell death. Mechanistically, high cystine uptake in cancer cells with high overexpression of SLC7A11 in combination with H₂O₂ treatment results in toxic buildup of intracellular cystine and other disulfide molecules, NADPH depletion, redox system collapse, and rapid cell death (likely disulfidptosis). We further show that high overexpr

SUBMITTER: Yan Y 

PROVIDER: S-EPMC10281978 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature