MTCH2 Deficiency Promotes E2F4/TFRC-Mediated Ferroptosis and Sensitizes Colorectal Cancer Liver Metastasis to Sorafenib.

ABSTRACT: Ferroptosis is a specific type of lipid peroxide-mediated cell death which is crucial in tumor suppression. While the mitochondrial carrier homolog 2 (MTCH2) is implicated in lipid homeostasis and mitochondrial metabolism, its role in ferroptosis and colorectal cancer (CRC) remains uncharacterized. Here, MTCH2 is identified as a crucial regulator of ferroptosis in CRC progression. Clinically, high expression of MTCH2 in CRC tissues predicts poor prognosis. Functionally, loss of MTCH2 inhibits azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colorectal tumorigenesis in MTCH2^cKO mice and leads to accumulation of ferrous ion and enhances ferroptosis of CRC in vitro and in vivo. Mechanistically, MTCH2 deficiency promotes the proteasome-dependent ubiquitination of E2F4 and att

SUBMITTER: Xing P 

PROVIDER: S-EPMC12463053 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature