Jennifer Noto
Last active: 11/30/2018

Helicobacter pylori bacteria alter the p53 stress response via ERK-HDM2 pathway.

Bhardwaj V, Noto JM, Wei J, Andl C, El-Rifai W, Peek RM, Zaika AI
Oncotarget. 2015 6 (3): 1531-43

PMID: 25605238 · PMCID: PMC4359312 · DOI:10.18632/oncotarget.2828

H. pylori infection is the strongest known risk factor for gastric cancer. Inhibition of host tumor suppressor mechanisms by the bacteria underlies the development of this disease. Among the tumor suppressors affected by H. pylori are p53 and E-cadherin, which inhibition has been shown to increase the risk of gastric cancer. In this report, we investigated the interaction between E-cadherin and p53 in H. pylori-infected cells. We found that downregulation of E-cadherin leads to cellular stress and activation of p53. In the setting of H. pylori infection, this mechanism, however, is disrupted. We found that although co-culture of gastric epithelial cells with H. pylori led to downregulation of E-cadherin and cellular stress, it resulted in inhibition of p53, which is mediated by intracellular Erk kinases and HDM2 protein induced by H. pylori. Experimental inhibition of HDM2/p53 interactions restored p53 activity, and decreased survival of infected cells. Collectively, our results revealed that regulation of p53 and E-cadherin is tightly linked through the p53 stress response mechanism that is inhibited by H. pylori via activation of Erk1/2-HDM2-p53 pathway leading to survival of damaged cells. This might be advantageous to the bacteria but may increase the cancer risk.

MeSH Terms (11)

Animals Cell Line, Tumor Gerbillinae Helicobacter Infections Helicobacter pylori Humans MAP Kinase Signaling System Proto-Oncogene Proteins c-mdm2 Stomach Neoplasms Transfection Tumor Suppressor Protein p53

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