CypA Mediates Non-Small Cell Lung Cancer Chemoresistance by Attenuating Ferroptosis via Stabilizing SLC7A11.

ABSTRACT: Non-small cell lung cancer (NSCLC) remains a major oncological challenge due to intrinsic or acquired chemoresistance, underscoring the urgent need to decipher novel regulatory mechanisms. Here, cyclophilin A (CypA) is identified as a critical mediator of cisplatin (DDP)/paclitaxel (DTX) resistance in NSCLC by suppressing ferroptosis, an iron-dependent form of regulated cell death. CypA is significantly overexpressed in DDP/DTX-resistant NSCLC cell lines and patient tissues, correlating with poor prognosis. Mechanistically, CypA stabilizes the ferroptosis suppressor SLC7A11 by competitively binding to its K37 site, blocking ubiquitination and proteasomal degradation mediated by the E3 ligase TRIM3. This interaction maintains cystine uptake, glutathione biosynthesis, and redox homeostasis,

SUBMITTER: Wang Z 

PROVIDER: S-EPMC12822425 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature