{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T03:21:00Z","timestamp":1784172060968,"version":"3.55.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T00:00:00Z","timestamp":1671753600000},"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":["81900500, 81870395, 82170580"],"award-info":[{"award-number":["81900500, 81870395, 82170580"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004479","name":"Natural Science Foundation of Jiangxi Province","doi-asserted-by":"publisher","award":["20212BAB216016"],"award-info":[{"award-number":["20212BAB216016"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004637","name":"Nanchang University","doi-asserted-by":"publisher","award":["4209-16100009-PY201923"],"award-info":[{"award-number":["4209-16100009-PY201923"]}],"id":[{"id":"10.13039\/501100004637","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>Helicobacter pylori<\/jats:italic> infection is the strongest known risk factor for gastric cancer. The Hippo signaling pathway controls organ size and maintains tissue homeostasis by coordinately regulating cell growth and proliferation. Here, we demonstrate the interactive role of TAZ, the transcriptional coactivator of the Hippo pathway, and beta-catenin in promoting the pathogenesis of <jats:italic>H. pylori<\/jats:italic> infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>TAZ expression was evaluated in human gastric tissues and <jats:italic>H. pylori<\/jats:italic>-infected insulin\u2013gastrin (INS-GAS) mice. Western blot, immunofluorescence, immunohistochemistry, and RT\u2013PCR assays were performed. Coimmunoprecipitation was performed to examine the interaction between TAZ and \u03b2-catenin. TAZ and \u03b2-catenin were silenced using small interfering RNAs. HA-\u03b2-catenin and Flag-TAZ were constructed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Increased TAZ was noted in human gastric cancer tissues compared to chronic gastritis tissues and in <jats:italic>H. pylori<\/jats:italic>-positive gastritis tissues compared to <jats:italic>H. pylori<\/jats:italic>-negative gastritis tissues. In addition, <jats:italic>H. pylori<\/jats:italic> infection induced TAZ expression and nuclear accumulation in the gastric tissue of INS-GAS mice and cultured gastric epithelial cells, which was dependent on the virulence factor CagA. Moreover, TAZ or \u03b2-catenin knockdown significantly suppressed <jats:italic>H. pylori<\/jats:italic> infection-induced cell growth, survival, and invasion. Furthermore, the interactive regulation of TAZ and \u03b2-catenin activation was revealed. Finally, \u03b2-catenin was required for <jats:italic>H. pylori<\/jats:italic>-induced TAZ activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings suggest the existence of a positive feedback loop of activation between TAZ and \u03b2-catenin that could play an important role in CagA+ <jats:italic>H. pylori<\/jats:italic> infection-induced gastric carcinogenesis. TAZ inhibition represents a potential target for the prevention of <jats:italic>H. pylori<\/jats:italic> infection-associated gastric cancer.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2022.1065462","type":"journal-article","created":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T04:50:48Z","timestamp":1671771048000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["A positive feedback loop of the TAZ\/\u03b2-catenin axis promotes Helicobacter pylori-associated gastric carcinogenesis"],"prefix":"10.3389","volume":"13","author":[{"given":"Xinbo","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunxi","family":"Shu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xidong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaobin","family":"Ouyang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingxing","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbo","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nonghua","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongming","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nianshuang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins11110677","article-title":"Helicobacter pylori virulence factors exploiting gastric colonization and its pathogenicity","volume":"11","author":"Ansari","year":"2019","journal-title":"Toxins (Basel)"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1053\/j.gastro.2010.06.047","article-title":"Tolerance rather than immunity protects from Helicobacter pylori-induced gastric preneoplasia","volume":"140","author":"Arnold","year":"2011","journal-title":"Gastroenterology"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.cell.2014.06.013","article-title":"YAP\/TAZ incorporation in the beta-catenin destruction complex orchestrates the Wnt response","volume":"158","author":"Azzolin","year":"2014","journal-title":"Cells"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.1016\/j.cell.2012.11.027","article-title":"Role of TAZ as mediator of Wnt signaling","volume":"151","author":"Azzolin","year":"2012","journal-title":"Cells"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1430","DOI":"10.1002\/hep.31120","article-title":"Cooperation between MYC and beta-catenin in liver tumorigenesis requires yap\/Taz","volume":"72","author":"Bisso","year":"2020","journal-title":"Hepatology"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1716","DOI":"10.1053\/j.gastro.2022.01.046","article-title":"Helicobacter pylori-induced RASAL2 through activation of nuclear factor-kappaB promotes gastric tumorigenesis via beta-catenin signaling Axis","volume":"162","author":"Cao","year":"2022","journal-title":"Gastroenterology"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"e12544","DOI":"10.1111\/hel.12544","article-title":"Helicobacter pylori VacA, a distinct toxin exerts diverse functionalities in numerous cells: an overview","volume":"24","author":"Chauhan","year":"2019","journal-title":"Helicobacter"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1128\/CMR.00011-10","article-title":"Helicobacter pylori infection and gastric adenocarcinoma","volume":"7","author":"Correa","year":"2011","journal-title":"US Gastroenterol. 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