Helicobacter pylori bacteria alter the p53 stress response via Erk-HDM2 pathway
| Autor: | Jinxiong Wei, Alexander Zaika, Richard M. Peek, Claudia D. Andl, Vikas Bhardwaj, Wael El-Rifai, Jennifer M. Noto |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
p53
MAPK/ERK pathway MAP Kinase Signaling System gastric tumor Transfection Helicobacter Infections Downregulation and upregulation Stomach Neoplasms Cell Line Tumor medicine Animals Humans CagA Helicobacter pylori biology Kinase Cancer Proto-Oncogene Proteins c-mdm2 biology.organism_classification medicine.disease 3. Good health Oncology Cell culture Cancer research HDM2 Tumor Suppressor Protein p53 Gerbillinae Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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