The CHPT-pSTAT3-SLC7A11 signaling axis controls progression and ferroptosis susceptibility of pancreatic cancer.

ABSTRACT:

Background

Pancreatic ductal adenocarcinoma (PDAC) exhibits profound chemoresistance and metastasis, driving its dismal prognosis. Gemcitabine (GEM) resistance remains a critical barrier, necessitating exploration of metabolic regulators like choline phosphotransferase 1 (CHPT1) and ferroptosis in PDAC therapy.

Method

GEM-resistant PDAC cells were generated through stepwise induction. Metabolomics, RNA sequencing, and functional assays (CCK-8, EdU, Transwell) identified CHPT's role. CHPT1 and SLC7A11 were genetically modulated using lentiviral vectors. Xenograft models assessed tumor growth.

Results

CHPT1 was downregulated in PDAC tissues and GEM-resistant cells. Restoring CHPT1 suppressed proliferation, migration, and epithelial-mesenchymal transition while enhancing

SUBMITTER: Yang J 

PROVIDER: S-EPMC12719990 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature