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Phosphorylation of the gastric tumor suppressor RUNX3 following H. pylori infection results in its localization to the cytoplasm
Author(s) -
Cinghu Senthilkumar,
Goh YunMi,
Oh ByungChul,
Lee YouSoub,
Lee OkJun,
Devaraj Halagowder,
Bae SukChul
Publication year - 2012
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22820
Subject(s) - intestinal metaplasia , pathogenesis , suppressor , cytoplasm , carcinogenesis , biology , cancer research , stomach , phosphorylation , helicobacter pylori , immunology , medicine , cancer , microbiology and biotechnology , genetics
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. J. Cell. Physiol. 227: 1071–1080, 2012. © 2011 Wiley Periodicals, Inc.