{"title":"GLIS2 Promotes Epithelial-Mesenchymal Transition and Gastric Cancer Progression by Regulating BGN to Activate the Wnt/β-Catenin Pathway.","authors":"Juan Yan, Ya-Peng Deng","doi":"10.1002/kjm2.70103","DOIUrl":null,"url":null,"abstract":"<p><p>This study elucidates the mechanism by which GLIS Family Zinc Finger 2 (GLIS2) promotes epithelial-mesenchymal transition (EMT) in gastric cancer through biglycan (BGN) activation and Wnt/β-catenin stimulation. By analyzing 18 pairs of GC tissues and establishing in vitro models (combining GLIS2 knockdown/BGN overexpression with Wnt pathway modulators), we demonstrated that GLIS2 directly binds to the BGN promoter to enhance its transcription, thereby activating Wnt/β-catenin signaling and significantly promoting GC cell migration, invasion, and EMT. Functional rescue experiments confirmed that BGN overexpression reverses the inhibitory effects of GLIS2 knockdown, while the Wnt/β-catenin inhibitor XAV-939 effectively blocks BGN's tumor-promoting effects. These findings establish the crucial role of the GLIS2-BGN-Wnt/β-catenin axis in regulating GC EMT and identify novel potential therapeutic targets for GC treatment.</p>","PeriodicalId":94244,"journal":{"name":"The Kaohsiung journal of medical sciences","volume":" ","pages":"e70103"},"PeriodicalIF":3.1000,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Kaohsiung journal of medical sciences","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1002/kjm2.70103","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
This study elucidates the mechanism by which GLIS Family Zinc Finger 2 (GLIS2) promotes epithelial-mesenchymal transition (EMT) in gastric cancer through biglycan (BGN) activation and Wnt/β-catenin stimulation. By analyzing 18 pairs of GC tissues and establishing in vitro models (combining GLIS2 knockdown/BGN overexpression with Wnt pathway modulators), we demonstrated that GLIS2 directly binds to the BGN promoter to enhance its transcription, thereby activating Wnt/β-catenin signaling and significantly promoting GC cell migration, invasion, and EMT. Functional rescue experiments confirmed that BGN overexpression reverses the inhibitory effects of GLIS2 knockdown, while the Wnt/β-catenin inhibitor XAV-939 effectively blocks BGN's tumor-promoting effects. These findings establish the crucial role of the GLIS2-BGN-Wnt/β-catenin axis in regulating GC EMT and identify novel potential therapeutic targets for GC treatment.
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