title: Phosphorylation of the gastric tumor suppressor RUNX3 following H. pylori infection results in its localization to the cytoplasm.
abstract: As H. pylori infection progresses, intestinal metaplasia (IM), a key event in gastric carcinogenesis, develops in the stomach. The mechanism by which H. pylori infection causes the trans-differentiation of gastric cells to intestinal-type cells remains an important question. In the current study, we found that RUNX3 is deregulated in all human IM specimens examined by either down regulation or mislocalization; Aberrant localization of a gastric tumor suppressor RUNX3 is observed in most human cases of IM with concurrent H. pylori infection, and RUNX3 is down-regulated in most cases of IM without H. pylori-infection. The cytoplasmic mislocalization of a RUNX3 was associated with H. pylori-induced c-Src activation and RUNX tyrosine phosphorylation. Moreover, gastric epithelial cells of Runx3(-/-) mice expressed the intestinal markers Muc2 and Li-Cadherin, which suggests that the deregulation of Runx3 is a key event in the intestinalization of the gastric epithelium. Collectively, the results of the current study suggest that RUNX3 deregulation is associated with H. pylori-induced pathogenesis and the development of IM.
authors.affiliation: Department of Biochemistry, School of Medicine, Institute for Tumor Research, Chungbuk National University, Cheongju, South Korea.
authors.forename: Senthilkumar
authors.initials: S
authors.lastname: Cinghu
authors.forename: Yun-Mi
authors.initials: YM
authors.lastname: Goh
authors.forename: Byung-Chul
authors.initials: BC
authors.lastname: Oh
authors.forename: You-Soub
authors.initials: YS
authors.lastname: Lee
authors.forename: Ok-Jun
authors.initials: OJ
authors.lastname: Lee
authors.forename: Halagowder
authors.initials: H
authors.lastname: Devaraj
authors.forename: Suk-Chul
authors.initials: SC
authors.lastname: Bae
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D005756:Gastritis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016481:Helicobacter Infections / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation / Q000235:genetics; D013274:Stomach Neoplasms / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; C493730:Runx3 protein, mouse