2. Academic Validation
  3. FASN promotes lipid metabolism and progression in colorectal cancer via the SP1/PLA2G4B axis

FASN promotes lipid metabolism and progression in colorectal cancer via the SP1/PLA2G4B axis

  • Cell Death Discov. 2025 Mar 28;11(1):122. doi: 10.1038/s41420-025-02409-9.
Xin Liu 1 2 3,  Jiachun Lu 1 2 3,  Xiangyu Ni 1 2 3,  Yuxin He 1 2 3,  Jiayu Wang 1 2 3,  Zilin Deng 1 2 3,  Guangbo Zhang 1 3,  Tongguo Shi 4,  Weichang Chen 5 6
Affiliations

Affiliations

  • 1 Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, China.
  • 2 Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China.
  • 3 Jiangsu Key Laboratory of Clinical Immunology, Soochow University, Suzhou, China.
  • 4 Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, China. shitg@suda.edu.cn.
  • 5 Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China. weichangchen@126.com.
  • 6 Jiangsu Key Laboratory of Clinical Immunology, Soochow University, Suzhou, China. weichangchen@126.com.
PMID: 40148316 DOI: 10.1038/s41420-025-02409-9
Abstract

Abnormal metabolic reprogramming is essential for tumorigenesis, metastasis, and the regulation of immune responses. Fatty acid synthase (FASN), a key enzyme in lipid metabolism, plays a crucial role in these processes. However, the relationship between FASN-mediated lipid reprogramming and the immune response in colorectal Cancer (CRC) remains unclear. The present study demonstrated that FASN expression is elevated in CRC tissues and is significantly associated with poor prognosis. Functional experiments revealed that FASN promotes proliferation, migration, invasion, and phosphatidylcholine (PC) production in CRC cells. Additionally, in vivo experiments revealed that FASN knockdown significantly inhibits tumor growth and the spread of CRC cells to the lungs. Mechanistically, FASN, which is upregulated in CRC tissues, drives Cancer cell proliferation, metastasis, and PC metabolism through the SP1/PLA2G4B axis, subsequently suppressing the antitumor response of natural killer (NK) cells in a PC-dependent manner. These findings provide new insights into lipid metabolism and the immunobiology of CRC, suggesting potential targets for the treatment and prevention of CRC. Schematic diagram showing the mechanism by which FASN promotes Cancer cell proliferation, metastasis, and PC metabolism in CRC via the SP1/PLA2G4B axis, subsequently suppressing the antitumor response of NK cells in a PC-dependent manner. FFA free fatty acid, LPA lysophosphatidic acid, PA phosphatidate, DAG diglyceride, PC phosphatidylcholine, LPC lysophosphatidylcholine, CE Cholesterol ester, TAG triacylglycerol.

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