{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T17:46:53Z","timestamp":1791740813173,"version":"4.3.4"},"reference-count":57,"publisher":"Wiley","issue":"28","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Peritoneal metastasis is the most lethal manifestation of gastric cancer, with a median survival of less than one year, highlighting the need for new therapeutic targets. Through an in vivo genome\u2010wide CRISPR\/Cas9 screen, we identified GRIA2, an AMPA\u2010type glutamate receptor subunit, as a key driver of peritoneal metastasis. GRIA2 promotes gastric cancer cell migration, invasion, stemness, and adhesion to mesothelial cells in a glutamate\u2010dependent manner. Mechanistically, glutamate activates GRIA2, enhancing its interaction with GSK\u20103\u03b2 and inducing calcium influx, inhibiting GSK\u20103\u03b2 kinase activity and stabilizing \u03b2\u2010catenin, thereby activating the Wnt\/\u03b2\u2010catenin signaling pathway. Single\u2010cell RNA sequencing revealed that cancer\u2010associated fibroblasts are the primary source of glutamate in the peritoneal microenvironment, which establishes a paracrine axis that enhances GRIA2\u2010driven metastasis. Pharmacological inhibition of AMPA receptors with NBQX and Selurampanel suppressed peritoneal metastasis in both cell line\u2010derived and patient\u2010derived organoid xenograft (PDOX) mouse models. In clinical analysis, GRIA2 expression in peritoneal metastases correlated with the levels of \u03b2\u2010catenin and phosphorylated GSK\u20103\u03b2 (serine 9), with high GRIA2 expression predicting poor prognosis. These findings suggest that GRIA2 is a novel therapeutic target, and AMPA receptor antagonists are promising agents for treating gastric cancer peritoneal metastasis.<\/jats:p>","DOI":"10.1002\/advs.202521746","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T15:39:25Z","timestamp":1773157165000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["In Vivo CRISPR Screening Identifies the Glutamate Receptor GRIA2 as Promoting Peritoneal Metastasis of Gastric Cancer via Calcium\u2010Dependent \u03b2\u2010Catenin Activation"],"prefix":"10.1002","volume":"13","author":[{"given":"Jie","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Surgery Zhongshan Hospital Fudan University  Shanghai China"},{"name":"Cancer Center Zhongshan Hospital Fudan University  Shanghai China"},{"name":"Gastric Cancer Center Zhongshan Hospital, Fudan University  Shanghai 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