biostudies-literatureLi KNatural Science Foundation of Liaoning Province (Liaoning Provincial Natural Science Foundation)Natural Science Foundation of Liaoning ProvinceChina Health and Medical Development Foundation1480https://www.ebi.ac.uk/biostudies/studies/S-EPMC12534568biostudies-literatureUnknown8(1)Metabolic reprogramming is one of the hallmark events in colorectal cancer. Tumor cells adapt to microenvironmental changes by regulating energy and biomaterial metabolism. This study identifys abnormal lipid accumulation and significant downregulation of fatty acid metabolism in colorectal cancer. The core gene of this pathway, CPT2, critically impacts colorectal cancer patient survival and regulates tumor cell proliferation both in vitro and in vivo. Metabolite analysis demonstrates that CPT2 knockdown induced accumulation of glycerophospholipids, primarily phosphatidylcholine and phosphatidylethanolamine, driven by enhanced long-chain fatty acid-dependent glycerophospholipid biosynthesis mediated by GPAT4. Transcriptomic analysis and subsequent experiments reveal that glycerophospholipiCommunications biologyCPT2 inhibition enhances selective autophagy and proliferation in colorectal cancer via GPAT4-dependent glycerophospholipid biosynthesis.PMC125345682023-BSBA-1792021-MS-058Li GLi JLi CLiu MCui WFu YWang HLi KXiao MChen WLuo YShen SWei HShao RZhao JfalseCPT2 inhibition enhances selective autophagy and proliferation in colorectal cancer via GPAT4-dependent glycerophospholipid biosynthesis.Metabolic reprogramming is one of the hallmark events in colorectal cancer. Tumor cells adapt to microenvironmental changes by regulating energy and biomaterial metabolism. This study identifys abnormal lipid accumulation and significant downregulation of fatty acid metabolism in colorectal cancer. The core gene of this pathway, CPT2, critically impacts colorectal cancer patient survival and regulates tumor cell proliferation both in vitro and in vivo. Metabolite analysis demonstrates that CPT2 knockdown induced accumulation of glycerophospholipids, primarily phosphatidylcholine and phosphatidylethanolamine, driven by enhanced long-chain fatty acid-dependent glycerophospholipid biosynthesis mediated by GPAT4. Transcriptomic analysis and subsequent experiments reveal that glycerophospholipi2025-01-01T00:00:00Z2025 Oct2026-06-04T14:30:03.06Z2026-05-10T03:11:34.256ZS-EPMC125345684110745810.1038/s42003-025-08877-0