{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T06:19:13Z","timestamp":1787897953397,"version":"build-2784847793"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca corrente linea 1"],"award-info":[{"award-number":["Ricerca corrente linea 1"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Progetto di Ricerca Finalizzata 5\u2030 2018"],"award-info":[{"award-number":["Progetto di Ricerca Finalizzata 5\u2030 2018"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Gastric Cancer"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>EMILIN-1 is an extracellular matrix glycoprotein with tumor-suppressive functions. While its loss is implicated in cancer progression, its specific role in the gastric tumor microenvironment and its clinical relevance remain poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using in vitro cellular systems and genetically modified mouse models we investigated the consequences of impaired EMILIN-1 function on gastric epithelial transformation, stromal remodeling, and fibroblast reprogramming. Histopathological analysis, gene expression profiling, and functional assays were employed to assess phenotypic changes in epithelial, fibroblastic, and endothelial compartments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that gastric cancer (GC) cells downregulate EMILIN-1 in stromal fibroblasts and lymphatic endothelial cells via paracrine signaling, leading to reduced EMILIN-1 deposition and disrupted lymphatic organization. Mechanistically, the interaction between EMILIN-1 and \u03b14\u03b21 integrin, which is absent in GC cells, modulates tumor cell proliferation; loss of this axis allows tumor cells to escape ECM-mediated growth control. Furthermore, EMILIN-1 downregulation reprograms fibroblasts into a pro-tumorigenic phenotype, which enhances GC cell migration and clonogenic potential. EMILIN-1 loss-of-function (E955A) mice showed increased susceptibility to pre-neoplastic lesions, a finding mirrored in human dysplastic tissues where EMILIN-1 was markedly reduced.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings establish EMILIN-1 as a master regulator of gastric tissue integrity. Its loss creates a tumor-permissive microenvironment by disrupting epithelial homeostasis, impairing lymphatic structure, and promoting fibroblast activation. The consistent reduction of EMILIN-1 in early human dysplasia highlights its potential as a novel stromal biomarker for early GC risk stratification. Moreover, restoring the EMILIN-1\/integrin axis represents a promising therapeutic strategy to re-establish growth control and suppress tumor progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10120-026-01781-4","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T09:20:13Z","timestamp":1784539213000},"page":"987-1000","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Loss of EMILIN-1\/integrin axis drives microenvironmental reprogramming in gastric tumorigenesis"],"prefix":"10.1007","volume":"29","author":[{"given":"Alessandra","family":"Capuano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maddalena","family":"Vescovo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samanta","family":"Muzzin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrica","family":"Timis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Cesaratto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliana","family":"Pivetta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Doliana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Palumbo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato","family":"Cannizzaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Canzonieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenio","family":"Scanziani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Canesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Baldassarre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Mongiat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3033-404X","authenticated-orcid":false,"given":"Paola","family":"Spessotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"1781_CR1","doi-asserted-by":"publisher","first-page":"2452","DOI":"10.3748\/wjg.v29.i16.2452","volume":"29","author":"W-J Yang","year":"2023","unstructured":"Yang W-J, Zhao H-P, Yu Y, Wang J-H, Guo L, Liu J-Y, et al. 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Informed consent to be included in the study, or the equivalent, was obtained from all patients.","order":2,"name":"Ethics","label":"Ethical statement","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All institutional and national guidelines for the care and use of laboratory animals were followed.","order":3,"name":"Ethics","label":"Human and animals","group":{"name":"EthicsHeading","label":"Declarations"}}]}}