{"title":"GLIS2通过调节BGN激活Wnt/β-Catenin通路促进上皮-间质转化和胃癌进展。","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":"{\"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}","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}
GLIS2 Promotes Epithelial-Mesenchymal Transition and Gastric Cancer Progression by Regulating BGN to Activate the Wnt/β-Catenin Pathway.
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.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
