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Here, we performed an integrated single\u2010cell analysis of gastric cancer primary tumours and their corresponding liver and lymph node metastases to identify critical intercellular communication networks driving the metastatic process. Notably, gene expression analysis of metastatic tissues showed significant upregulation of cholesterol metabolism and PPAR signalling pathway (a nuclear receptor\u2013mediated regulatory system that orchestrates lipid metabolism, adipogenesis and energy homeostasis) genes compared to primary tumours. Our analysis revealed that myeloid cell\u2013derived Galectin\u20109 (LGALS9) and its receptor beta\u2010subunit of prolyl 4\u2010hydroxylase (P4HB) on epithelial cells constitute a previously uncharacterized ligand\u2013receptor interaction involved in gastric cancer metastasis. Functional experiments confirmed that the activation of P4HB by LGALS9 significantly enhanced proliferation, epithelial\u2010mesenchymal transition (EMT) and lipid metabolism in gastric cancer cells, while pharmacological inhibition of P4HB reversed these effects. Collectively, our findings establish the myeloid\u2010derived LGALS9\u2010P4HB interaction as a crucial mediator of gastric cancer metastatic colonisation through modulation of lipid metabolism, suggesting a potential therapeutic target for metastatic gastric cancer.<\/jats:p>","DOI":"10.1111\/jcmm.70661","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T04:59:15Z","timestamp":1750309155000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Myeloid\u2010Derived <scp>LGALS9<\/scp>\u2010<scp>P4HB<\/scp> Immune Interaction Promotes Metastasis in Gastric Cancer Through Enhanced Cell Proliferation and Lipid Metabolism"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5516-9215","authenticated-orcid":false,"given":"Xiaobin","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Spine Surgery and Musculoskeletal Tumor Zhongnan Hospital 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