{"title":"FASN promotes lipid metabolism and progression in colorectal cancer via the SP1/PLA2G4B axis.","authors":"Xin Liu, Jiachun Lu, Xiangyu Ni, Yuxin He, Jiayu Wang, Zilin Deng, Guangbo Zhang, Tongguo Shi, Weichang Chen","doi":"10.1038/s41420-025-02409-9","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"122"},"PeriodicalIF":6.1000,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950308/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Death Discovery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41420-025-02409-9","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍：
Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary.
Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.
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