Atorvastatin promotes lipid catabolism in colorectal cancer via FDFT1‒mediated inhibition of the PI3K/AKT pathway

  • Cell Commun Signal. 2026 Mar 23;24(1):259. doi: 10.1186/s12964-026-02802-6.
Jiale Xu  1 ,  Xiaoyu Qin  1 ,  Longying Xiong  2 ,  Cheng Zhao  2 ,  Dan Ge  2 ,  Yanping Wu  2 ,  Yixuan Shen  2 ,  Mengli Yang  2 ,  Bihan Shen  2 ,  Min Chen  1 ,  Chen Min  3
Affiliations
  • 1. Department of Gastroenterology, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing University of Chinese Medicine, Nanjing City, 210008, Jiangsu Province, P.R. China.
  • 2. Department of Gastroenterology, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing University, Nanjing City, 210008, Jiangsu Province, P.R. China.
  • 3. Department of Gastroenterology, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing University of Chinese Medicine, Nanjing City, 210008, Jiangsu Province, P.R. China. [email protected].
PMID: 41866501 DOI: 10.1186/s12964-026-02802-6
Abstract

As a hydroxymethylglutaryl‒coenzyme A reductase (HMGCR) inhibitors, atorvastatin (ATST) has garnered widespread attention because of its antitumor effects. However, its specific mechanism of action remains incompletely understood. In our study, ATST was found to inhibit AOM/DSS‒induced colorectal Cancer (CRC) progression in mice. Mechanistically, by inhibiting HMGCR and depleting cellular Cholesterol, ATST activates the SREBP2‒FDFT1 axis. This in turn inhibits the PI3K/Akt pathway, inducing endoplasmic reticulum (ER) stress and Autophagy while concurrently promoting lipid catabolism to drive Ferroptosis. This study elucidates the mechanism through which ATST regulates lipid catabolism to influence CRC progression, providing a new direction for CRC therapy.

Supplementary Information: The online version contains supplementary material available at 10.1186/s12964-026-02802-6.

Keywords
Atorvastatin; Colorectal cancer; ER stress; FDFT1; Lipid catabolism; PI3K/AKT pathway.
Products