{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T09:18:48Z","timestamp":1788167928841,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82403094"],"award-info":[{"award-number":["82403094"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2026,5,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Gastric cancer (GC) is the fifth most diagnosed malignancy and the fifth leading cause of cancer\u2010related deaths, with a poor overall survival of under one year. Metastatic tumors that arise from malignant primary tumors account for the majority of cancer\u2010related deaths for GC. Hypoxia\u2010inducible transcription factors (HIFs), including HIF\u20102\u03b1, and integrin such as ITG\u03b25 play important roles in tumor metastasis. However, the regulatory relationship and functional significance between HIF\u20102\u03b1 and ITG\u03b25 in GC remain poorly understood. We analyzed TCGA RNA\u2010seq data to identify hypoxia\u2010related biological processes and signaling pathways in GC. Exosome proteomics was used to characterize the protein profiles of extracellular vesicles (EVs) derived from GC cells under hypoxia. Under hypoxic conditions, ITG\u03b25 expression in GC showed a positive correlation with HIF\u20102\u03b1 levels. Clinical analysis confirmed the overexpression of ITG\u03b25, which was further validated by RT\u2010qPCR, western blot, and flow cytometry. The chromatin immunoprecipitation (ChIP) was performed to confirm the binding of HIF\u20102\u03b1 to the promoter of ITG\u03b25. The role of ITG\u03b25 in GC cell proliferation, invasion, and migration was investigated through gain\u2010 and loss\u2010of\u2010function studies conducted both in\u00a0vivo and in\u00a0vitro. Our results showed that HIF\u20102\u03b1 directly binds to the promoter of ITG\u03b25, thereby transcriptionally activating its expression. In\u00a0vivo and in\u00a0vitro studies revealed that the overexpression of ITG\u03b25 significantly enhanced the invasion, migration, and growth of GC. Our study uncovers a novel pathway in which hypoxia\u2010induced activation of HIF\u20102\u03b1 promotes the proliferation, invasion, and metastasis of GC by directly upregulating the expression of exosomal ITG\u03b25. Given these findings, ITG\u03b25 may serve as a potential prognostic biomarker and therapeutic target for GC.<\/jats:p>","DOI":"10.1096\/fj.202600482r","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T03:59:01Z","timestamp":1778039941000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hypoxia\u2010Driven\n                    <scp>HIF<\/scp>\n                    \u20102\u03b1 Transcriptionally Activates Exosomal\n                    <scp>ITG\u03b25<\/scp>\n                    to Promote Gastric Cancer Progression"],"prefix":"10.1096","volume":"40","author":[{"given":"Chao","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Geriatric Gastroenterology The First Affiliated Hospital of Nanjing Medical University  Nanjing China"},{"name":"Department of Biotherapy The Second Affiliated Hospital of Nanjing Medical University  Nanjing China"},{"name":"Department of 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