{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T12:58:07Z","timestamp":1790600287865,"version":"4.1.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62373370"],"award-info":[{"award-number":["62373370"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Gastric cancer (GC) remains a major cause of cancer-related mortality, and the molecular drivers underlying GC progression require further clarification. SLC12A7 has been implicated in several malignancies, but its clinical significance and biological function in GC remain incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the clinical significance and functional role of SLC12A7 in GC and to explore whether Ezrin-associated PI3K\/AKT signaling is involved in SLC12A7-mediated malignant phenotypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>TCGA-STAD RNA-seq data, GEO datasets (GSE29272, GSE3438, and GSE66229), and tissue microarrays were integrated to evaluate SLC12A7 expression and its clinicopathological relevance in Gastric cancer. STRING analysis, molecular docking, and immunofluorescence colocalization were used to assess the potential association between SLC12A7 and Ezrin. Functional assays, including siRNA-mediated knockdown, Ezrin re-expression, CCK-8, Transwell, flow cytometry, qRT-PCR, and Western blotting, were performed to examine proliferation, migration, invasion, cell-cycle distribution, apoptosis, EMT-associated markers, and PI3K\/AKT signaling in GC\u00a0cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      SLC12A7 was upregulated in GC tissues and cell lines and was associated with selected clinicopathological characteristics and shorter survival.\n                      <jats:italic>SLC12A7<\/jats:italic>\n                      knockdown suppressed GC-cell proliferation, migration, and invasion, induced G2\/M cell-cycle arrest and apoptosis, reduced PI3K\/AKT phosphorylation, increased E-cadherin, cleaved caspase-3, and cleaved caspase-9, and decreased vimentin, cyclin A2, and CDK1.\n                      <jats:italic>SLC12A7<\/jats:italic>\n                      expression was positively correlated with Ezrin expression, and partial colocalization of\n                      <jats:italic>SLC12A7<\/jats:italic>\n                      and Ezrin was observed in GC\u00a0cells. Ezrin re-expression partially restored PI3K\/AKT phosphorylation and attenuated the inhibitory effects caused by\n                      <jats:italic>SLC12A7<\/jats:italic>\n                      knockdown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>SLC12A7<\/jats:italic>\n                      may promote malignant phenotypes in GC\u00a0cells through an Ezrin-associated PI3K\/AKT signaling mechanism, supporting its potential value as a biomarker and therapeutic target in GC.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1828288","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:35:44Z","timestamp":1789450544000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["SLC12A7 promotes malignant phenotypes of gastric cancer cells and is associated with Ezrin-related PI3K\/AKT signaling"],"prefix":"10.3389","volume":"14","author":[{"given":"Zhijian","family":"Li","sequence":"first","affiliation":[{"name":"Department of General Surgery, Shengjing Hospital of China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology, China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tangyi","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Shengjing Hospital of China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songhe","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Shengjing Hospital of China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianbiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology, China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Shengjing Hospital of China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.mam.2012.05.002","article-title":"The SLC12 family of electroneutral cation-coupled chloride cotransporters","volume":"34","author":"Arroyo","year":"2013","journal-title":"Mol. 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