| First Author | Liu F | Year | 2020 |
| Journal | J Exp Med | Volume | 217 |
| Issue | 1 | PubMed ID | 31645367 |
| Mgi Jnum | J:285061 | Mgi Id | MGI:6392723 |
| Doi | 10.1084/jem.20182325 | Citation | Liu F, et al. (2020) Core 1-derived mucin-type O-glycosylation protects against spontaneous gastritis and gastric cancer. J Exp Med 217(1) |
| abstractText | Core 1-derived mucin-type O-glycans (O-glycans) are a major component of gastric mucus with an unclear role. To address this, we generated mice lacking gastric epithelial O-glycans (GEC C1galt1-/-). GEC C1galt1-/- mice exhibited spontaneous gastritis that progressed to adenocarcinoma with approximately 80% penetrance by 1 yr. GEC C1galt1-/- 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-/- stomach were concurrent with activation of caspases 1 and 11 (Casp1/11)-dependent inflammasome. GEC C1galt1-/- 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. |
