Pharmacological induction of acetyl-CoA carboxylase 1 autophagic degradation attenuates lipid accumulation and cholangiocarcinoma progression.

ABSTRACT:

Background

Aberrant glycogen metabolism drives lipid accumulation and adaptive lipid homeostasis reprogramming, a metabolic adaptation critical for sustaining malignant progression and chemoresistance in cholangiocarcinoma (CCA). While our prior study highlighted glycogen degradation as pivotal for CCA tumorigenesis, the molecular mechanisms governing lipogenesis and its therapeutic exploitation remain elusive.

Methods

We performed single-cell RNA sequencing to explore metabolic status in CCA. A high-throughput screening of 994 bioactive compound library was performed to identify pharmacological agents capable of inhibiting CCA and targeting this metabolic vulnerability. The drug efficacy was demonstrated through in vitro and in vivo experiments. Additionally, a biotinylated

SUBMITTER: Pan Y 

PROVIDER: S-EPMC12645744 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature