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 H 2 O 2 , a common oxidative stress inducer, its high overexpression dramatically increases H 2 O 2 -induced cell death. Mechanistically, high cystine uptake in cancer cells with high overexpression of SLC7A11 in combination with H 2 O 2 treatment results in toxic buildup of intracellular cystine and other disulfide molecules, NADPH depletion, redox system collapse, and rapid cell death (likely disulfidptosis).…

• FF
  Foundation for the National Institutes of Health

  Awards: R01CA269140, R01CA166051
• CP
  Cancer Prevention and Research Institute of Texas

  Awards: RP230072, RP220258
• EC
  Emerson Collective
• NI
  National Institutes of Health

  Awards: P30CA016672, R01CA269140, R01CA247992, R01CA269646, R01CA166051, R01CA181196, RP220258, U54CA274220, R01CA244144, RP230072
• UO
  University of Texas MD Anderson Cancer Center

  Awards: P30CA016672, RP230072