MUC1 drives ferroptosis resistance in ICC via Src-mediated FSP1 deubiquitination and myristoylation.

ABSTRACT:

Background

Intrahepatic cholangiocarcinoma (ICC) exhibits poor prognosis and limited therapeutic options. Ferroptosis represents a promising therapeutic strategy, yet resistance mechanisms remain poorly understood. This study investigated the role of mucin 1 (MUC1) in regulating ferroptosis sensitivity in ICC.

Methods

Bioinformatic analyses of GEO and TCGA datasets identified ferroptosis-related factors in ICC. MUC1 expression was validated in ICC cell lines and clinical specimens. Ferroptosis sensitivity was assessed through RSL3-induced cell death assays, lipid peroxidation measurements, and iron detection. Mechanistic studies employed immunoprecipitation-mass spectrometry, co-immunoprecipitation, kinase assays, and deubiquitination assays. In vivo efficacy was evaluated u

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC12510807 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature