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To address this, we generated mice lacking gastric epithelial O-glycans (GEC C1galt1\u2212\/\u2212). GEC C1galt1\u2212\/\u2212 mice exhibited spontaneous gastritis that progressed to adenocarcinoma with \u223c80% penetrance by 1 yr. GEC C1galt1\u2212\/\u2212 gastric epithelium exhibited defective expression of a major mucus forming O-glycoprotein Muc5AC relative to WT controls, which was associated with impaired gastric acid homeostasis. Inflammation and tumorigenesis in GEC C1galt1\u2212\/\u2212 stomach were concurrent with activation of caspases 1 and 11 (Casp1\/11)\u2013dependent inflammasome. GEC C1galt1\u2212\/\u2212 mice genetically lacking Casp1\/11 had reduced gastritis and gastric cancer progression. Notably, expression of Tn antigen, a truncated form of O-glycan, and CASP1 activation was associated with tumor progression in gastric cancer patients. These results reveal a critical role of O-glycosylation in gastric homeostasis and the protection of the gastric mucosa from Casp1-mediated gastric inflammation and cancer.<\/jats:p>","DOI":"10.1084\/jem.20182325","type":"journal-article","created":{"date-parts":[[2019,10,23]],"date-time":"2019-10-23T18:54:12Z","timestamp":1571856852000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":61,"title":["Core 1\u2013derived mucin-type O-glycosylation protects against spontaneous gastritis and gastric cancer"],"prefix":"10.1084","volume":"217","author":[{"given":"Fei","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China 1"},{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxin","family":"Fu","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirk","family":"Bergstrom","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xindi","family":"Shan","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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