FASN promotes the stemness of cancer stem cells and protects colorectal cancer cells from ferroptosis by inhibiting the activation of SREBP2.

ABSTRACT:

Introduction

Fatty acid synthase (FASN) is a key regulator of lipid metabolism, but its role in colorectal cancer (CRC) stemness and ferroptosis remains unclear.

Methods

FASN expression in CRC was analyzed using TCGA data and validated in CRC cell lines (CACO-2, HCT116, SW480) and normal HIEC-6 cells via qRT-PCR and Western blot. HCT116 cells (highest FASN expression) were used for experiments. FASN silencing (shRNA) effects on CSCs were assessed via 3D spheroid formation and CD133+CD44+ flow cytometry. In vivo tumor growth was tested in BALB/c nude mice. Mechanistic assays included cholesterol detection, SREBP2 Western blot, fatostatin rescue experiments, ferroptosis markers (ferrous ions, ROS, MDA, 4-HNE, mitochondrial function), and FASN-SREBP2 co-immunoprecipitation.

SUBMITTER: Wang M 

PROVIDER: S-EPMC12399527 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature