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Review
. 2011 Feb;112(2):381-6.
doi: 10.1002/jcb.22964.

New insights into the inactivation of gastric tumor suppressor RUNX3: the role of H. pylori infection

Ying-Hung Nicole Tsang  1 , Acacia Lamb, Lin-Feng Chen
Affiliations
Review

New insights into the inactivation of gastric tumor suppressor RUNX3: the role of H. pylori infection

Ying-Hung Nicole Tsang et al. J Cell Biochem. 2011 Feb.

Abstract

Runt-related transcription factor 3, or RUNX3, is a tumor suppressor in gastric cancer. Inactivation of RUNX3 is causally associated with the genesis of gastric cancer, since RUNX3 is frequently inactivated in gastric cancers by hemizygous deletion, hypermethylation of its promoter, or protein mislocalization. Infection with Helicobacter pylori is the strongest risk factor for the development of gastric cancer. Recent studies have indicated that H. pylori infection plays an important role in the inactivation of RUNX3, and that this inactivation contributes to the pathogenesis of H. pylori. Here we summarize these recent advances and discuss their significances in understanding the initiation and development of gastric cancer.

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Figures

Fig. 1
Fig. 1
Inactivation of tumor suppressor RUNX3 by H. pylori infection. (A) CagA-dependent inactivation of RUNX3 by proteolytic degradation. CagA is injected into host epithelial cells after H. pylori infection. Within the cells, it interacts with the Py motif of RUNX3 via its WW domain. Binding of CagA to RUNX3 recruits an unidentified E3 ubiquitin ligase and triggers the proteasome-mediated degradation of RUNX3. This rapid inactivation of RUNX3 during the early stage of infection might promote the proliferation and survival of gastric epithelial cells and the growth of the H. pylori. (B) Inactivation of RUNX3 by hypermethylation of the runx3 promoter. H. pylori infection induces the hypermethylation of the runx3 promoter. This epigenetic-level inactivation of RUNX3 is associated with H. pylori infection-induced inflammation, which results in abnormal activity of DNMTs and the production of nitric oxide (NO). Solid arrow: known interaction or inactivation; arrow with question mark: proposed interaction; dashed arrow: activation through multiple steps. ○ =CpG, ●=mCpG.
See this image and copyright information in PMC

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