Data from: Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis

Exchange of extracellular cystine for intracellular glutamate by the
antiporter system xc− is implicated in numerous pathologies.
Pharmacological agents that inhibit system xc− activity with high potency
have long been sought, but have remained elusive. In this study, we report
that the small molecule erastin is a potent, selective inhibitor of system
xc−. RNA sequencing revealed that inhibition of cystine–glutamate exchange
leads to activation of an ER stress response and upregulation of CHAC1,
providing a pharmacodynamic marker for system xc− inhibition. We also
found that the clinically approved anti-cancer drug sorafenib, but not
other kinase inhibitors, inhibits system xc− function and can trigger ER
stress and ferroptosis. In an analysis of hospital records and adverse
event reports, we found that patients treated with sorafenib exhibited
unique metabolic and phenotypic alterations compared to patients treated
with other kinase-inhibiting drugs. Finally, using a genetic approach, we
identified new genes dramatically upregulated in cells resistant to
ferroptosis.