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Endothelial-specific molecule 1 (ESM1) was found to be significantly associated with gastric cancer peritoneal metastasis (GCPM); however, the biological functions and molecular mechanisms of ESM1 in regulating GCPM remain unclear. Herein, we demonstrated that ESM1 expression was significantly upregulated in gastric cancer tissues and positively correlated with platelet endothelial cell adhesion molecule-1 (CD31) levels. Moreover, clinical validation, in in vitro and in vivo experiments, confirmed that ESM1 promoted gastric cancer angiogenesis, eventually promoting gastric cancer peritoneal metastasis. Mechanistically, ESM1 promoted tumor angiogenesis by binding to c-Met on the vascular endothelial cell membrane. In addition, our results confirmed that ESM1 upregulated VEGFA, HIF1\u03b1, and MMP9 expression and induced angiogenesis by activating the MAPK\/ERK pathway. In conclusion, our findings identified the role of ESM1 in gastric cancer angiogenesis and GCPM, thus providing insights into the diagnosis and treatment of advanced gastric cancer.<\/jats:p>","DOI":"10.3390\/cancers16010194","type":"journal-article","created":{"date-parts":[[2023,12,31]],"date-time":"2023-12-31T04:51:51Z","timestamp":1703998311000},"page":"194","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["ESM1 Interacts with c-Met to Promote Gastric Cancer Peritoneal Metastasis by Inducing Angiogenesis"],"prefix":"10.3390","volume":"16","author":[{"given":"Jiaoyang","family":"Yang","sequence":"first","affiliation":[{"name":"Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gege","family":"Shu","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8503-4071","authenticated-orcid":false,"given":"Anqi","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weikang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotong","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongbao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA A Cancer J. 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