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Lipid metabolism acts as a non\u2010negligible regulator in epithelial\u2013mesenchymal transition (EMT), which is crucial for the metastasis of GC. As apolipoprotein C2 (APOC2) is a key activator of lipoprotein lipase for triglyceride metabolism, the exact mechanism of APOC2 remains largely unknown in GC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Tandem mass tags identified differentially expressed proteins between human PM and GC tissues, and showed that APOC2 overexpressed in PM tissues, which was further confirmed by immunoblotting, immunohistochemistry, and ELISA. Global gene expression changes were identified in <jats:italic>APOC2<\/jats:italic> knockdown cells via RNA\u2010sequencing. The role of APOC2 in lipid metabolism of GC cells was assessed via the Seahorse XF analyzer and lipid staining assays. The biological role of APOC2 in GC cells was determined by 3D Spheroid invasion, apoptosis, colony formation, wound healing, transwell assay, and mouse models. The interaction between APOC2 and CD36 was analyzed by co\u2010immunoprecipitation and biolayer interferometry. The underlying mechanisms were investigated using western blot technique.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>APOC2 overexpressed in GC PM tissues. Upregulation of APOC2 correlated with a poor prognosis in GC patients. APOC2 promoted GC cell invasion, migration, and proliferation via CD36\u2010mediated PI3K\/AKT\/mTOR signaling activation. Furthermore, APOC2\u2010CD36 axis upregulated EMT markers of GC cells via increasing the phosphorylation of PI3K, AKT, and mTOR. Knockdown either <jats:italic>APOC2<\/jats:italic> or <jats:italic>CD36<\/jats:italic> inhibited the malignant phenotype of cancer cells, and delayed GC PM progression in murine GC models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>APOC2 cooperates with CD36 to induce EMT to promote GC PM via PI3K\/AKT\/mTOR pathway. APOC2\u2010CD36 axis may be a potential target for the treatment of aggressive GC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.522","type":"journal-article","created":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T19:00:54Z","timestamp":1628535654000},"source":"Crossref","is-referenced-by-count":112,"title":["Apolipoprotein C\u2010II induces EMT to promote gastric cancer peritoneal metastasis via PI3K\/AKT\/mTOR pathway"],"prefix":"10.1002","volume":"11","author":[{"given":"Chao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of General Surgery, Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of General Surgery Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University  Nanjing 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