{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:16:09Z","timestamp":1785417369834,"version":"3.56.0"},"reference-count":30,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T00:00:00Z","timestamp":1777161600000},"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":"crossref","award":["8237195"],"award-info":[{"award-number":["8237195"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["8237195"],"award-info":[{"award-number":["8237195"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003819","name":"Hubei Provincial Natural Science Foundation for Distinguished Young Scholars","doi-asserted-by":"publisher","award":["2022CFA104"],"award-info":[{"award-number":["2022CFA104"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key Research and Development Program of Wuhan","award":["2024020802030159"],"award-info":[{"award-number":["2024020802030159"]}]},{"name":"Scientific Research Project Funding of Jianghan University","award":["2023ZDRC01"],"award-info":[{"award-number":["2023ZDRC01"]}]},{"award":["2023ZDRC01"],"award-info":[{"award-number":["2023ZDRC01"]}],"id":[{"id":"https:\/\/ror.org\/041c9x778","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Introduction: Gastric cancer is a prevalent and aggressive malignancy driven by complex signaling networks. Estrogen receptor-\u03b136 (ER-\u03b136), a membrane-localized receptor, mediates non-genomic signaling and promotes tumor progression. ER-\u03b136 can interact with epidermal growth factor receptor (EGFR) to activate downstream mitogen-activated protein kinase (MAPK) signaling, but the detailed mechanism in gastric cancer remains unclear. This study aimed to explore whether ER-\u03b136 promotes gastric cancer progression by regulating serum and glucocorticoid-regulated kinase 1 (SGK1)-mediated Erk1\/2 activation.Methods:We collected 53 human gastric adenocarcinoma specimens and detected ER-\u03b136 expression by immunohistochemistry. Bioinformatics analysis was used to identify ER-\u03b136-related kinases. Gastric cancer cell lines (SGC7901, HGC27, NCI-N87, and MFC) were used for in vitro studies. Western blotting, qRT-PCR, immunofluorescence, co-immunoprecipitation (Co-IP), wound healing, MTT, and Transwell invasion analyses, and nude mouse orthotopic tumor models were applied to investigate the function and mechanism of the ER-\u03b136\/SGK1\/Erk1\/2 axis. Results: ER-\u03b136 was positively expressed in 62.3% of gastric adenocarcinoma tissues and was associated with poor differentiation and prognosis. SGK1 was identified as a key kinase downstream of ER-\u03b136. ER-\u03b136, SGK1, and p-Erk1\/2 were co-upregulated in gastric cancer tissues and cells. ER-\u03b136 regulated Raf\/MEK1\/2\/Erk1\/2 phosphorylation in an SGK1-dependent manner. EGF-induced Erk1\/2 activation required both ER-\u03b136 and SGK1. Overexpression of ER-\u03b136 promoted the proliferation, migration, and invasion of gastric cancer cells, while SGK1 knockdown abolished these oncogenic effects. In vivo experiments confirmed that ER-\u03b136 promoted gastric tumor growth and EGFR\/Erk signaling, which was attenuated by SGK1 knockdown. Conclusions: ER-\u03b136 contributes to the malignant progression of gastric adenocarcinoma by activating the Erk1\/2 pathway through SGK1. The ER-\u03b136\u2013SGK1\u2013Erk1\/2 axis may serve as a novel therapeutic target for gastric cancer.<\/jats:p>","DOI":"10.3390\/cells15090787","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T13:32:22Z","timestamp":1777469542000},"page":"787","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Estrogen Receptor-\u03b136 Mediates EGFR-SGK1 Signaling-Related Erk Activation in Gastric Cancer"],"prefix":"10.3390","volume":"15","author":[{"given":"Yibo","family":"Zhang","sequence":"first","affiliation":[{"name":"Hubei Key Laboratory of Cognitive and Affective Disorders, School of Medicine, Jianghan University, No. 8 Sanjiaohu Road, Wuhan 430056, China"},{"name":"Institutes of Biomedical Sciences, School of Medicine, Jianghan University, No. 8 Sanjiaohu Road, Wuhan 430056, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Cognitive and Affective Disorders, School of Medicine, Jianghan University, No. 8 Sanjiaohu Road, Wuhan 430056, China"},{"name":"Institutes of Biomedical Sciences, School of Medicine, Jianghan University, No. 8 Sanjiaohu Road, Wuhan 430056, China"},{"name":"Department of Pathology and Pathophysiology, School of Medicine, Jianghan University, No. 8 Sanjiaohu Road, Wuhan 430056, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5049-0288","authenticated-orcid":false,"given":"Yifan","family":"Xiao","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Cognitive and Affective Disorders, School of Medicine, Jianghan University, No. 8 Sanjiaohu Road, Wuhan 430056, China"},{"name":"Institutes of Biomedical Sciences, School of Medicine, Jianghan University, No. 8 Sanjiaohu Road, Wuhan 430056, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubing","family":"Yang","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Cognitive and Affective Disorders, School of Medicine, Jianghan University, No. 8 Sanjiaohu Road, Wuhan 430056, China"},{"name":"Institutes of Biomedical Sciences, School of Medicine, Jianghan University, No. 8 Sanjiaohu Road, Wuhan 430056, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8448-2507","authenticated-orcid":false,"given":"Qingqing","family":"Xu","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Cognitive and Affective Disorders, School of Medicine, Jianghan University, No. 8 Sanjiaohu Road, Wuhan 430056, China"},{"name":"Institutes of Biomedical Sciences, School of Medicine, Jianghan University, No. 8 Sanjiaohu Road, Wuhan 430056, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Liu","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Cognitive and Affective Disorders, School of Medicine, Jianghan University, No. 8 Sanjiaohu Road, Wuhan 430056, China"},{"name":"Institutes of Biomedical Sciences, School of Medicine, Jianghan University, No. 8 Sanjiaohu Road, Wuhan 430056, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5609-4247","authenticated-orcid":false,"given":"Wenli","family":"Huang","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Cognitive and Affective Disorders, School of Medicine, Jianghan University, No. 8 Sanjiaohu Road, Wuhan 430056, China"},{"name":"Institutes of Biomedical Sciences, School of Medicine, Jianghan University, No. 8 Sanjiaohu Road, Wuhan 430056, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingshan","family":"Pi","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Cognitive and Affective Disorders, School of Medicine, Jianghan University, No. 8 Sanjiaohu Road, Wuhan 430056, China"},{"name":"Institutes of Biomedical Sciences, School of Medicine, Jianghan University, No. 8 Sanjiaohu Road, Wuhan 430056, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Xiong","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Cognitive and Affective Disorders, School of Medicine, Jianghan University, No. 8 Sanjiaohu Road, Wuhan 430056, China"},{"name":"Institutes of Biomedical Sciences, School of Medicine, Jianghan University, No. 8 Sanjiaohu Road, Wuhan 430056, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Cognitive and Affective Disorders, School of Medicine, Jianghan University, No. 8 Sanjiaohu Road, Wuhan 430056, China"},{"name":"Institutes of Biomedical Sciences, School of Medicine, Jianghan University, No. 8 Sanjiaohu Road, Wuhan 430056, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7415-6230","authenticated-orcid":false,"given":"Xiji","family":"Shu","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Cognitive and Affective Disorders, School of Medicine, Jianghan University, No. 8 Sanjiaohu Road, Wuhan 430056, China"},{"name":"Institutes of Biomedical Sciences, School of Medicine, Jianghan University, No. 8 Sanjiaohu Road, Wuhan 430056, China"},{"name":"Department of Pathology and Pathophysiology, School of Medicine, Jianghan University, No. 8 Sanjiaohu Road, Wuhan 430056, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7833-0497","authenticated-orcid":false,"given":"Yiyuan","family":"Xia","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Cognitive and Affective Disorders, School of Medicine, Jianghan University, No. 8 Sanjiaohu Road, Wuhan 430056, China"},{"name":"Institutes of Biomedical Sciences, School of Medicine, Jianghan University, No. 8 Sanjiaohu Road, Wuhan 430056, China"},{"name":"Department of Pathology and Pathophysiology, School of Medicine, Jianghan University, No. 8 Sanjiaohu Road, Wuhan 430056, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,26]]},"reference":[{"key":"ref_1","first-page":"e1635","article-title":"GASTRIC CANCER WITH POSITIVE EX-PRESSION OF ESTROGEN RECEPTOR ALPHA: A CASE SERIES FROM A SINGLE WESTERN CENTER","volume":"34","author":"Pereira","year":"2022","journal-title":"Arq. 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