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Tumorigenesis

The number of microbial cells is about 10 times larger than the number of eukaryotic cells in the human body. Enteric bacteria play an important role in the pathogenesis of cancer. Due to the complexity of the gut fl ora, identifi cation of the specifi c microbial agents contributing to colon cancer remains challenging. How bacterial products directly contribute to cancer is still unknown. Bacteria can modulate the host by secreting bacterial eff ector proteins to the host cells. AvrA is a pathogenic protein of enteric bacteria that infl uences eukaryotic cell pathways utilizing ubiquitin and acetylation. We hypothesize that the bacterial eff ector AvrA activates the STAT/beta-catenin pathway to promote colonic tumorigenesis. We investigated a chronic bacterial infected cancer model with Salmonella colonization in the mouse intestine. Mice were colonized with AvrA- suffi cient or defi cient bacterial strains, then stimulated with a carcinogen azoxymethane and dextran sodium sulfate (induced colitis). We found that mice infected with AvrA-expressed bacteria had signifi cantly high incidence of tumor in colon. AvrA expression decreased the phosphorylated-beta-catenin and inhibits the ubiquitination of beta-catenin in mouse colonic epithelial cells in vivo. Infl ammatory cytokines such as IL-6 and INF-gamma in serum were increased. Overall, AvrA activation of the STAT/beta-catenin pathway promoted colonic tumorigenesis. Th e current study provides important insights into intestinal infection and cancer stem cells. Our fi ndings can also be applied to the risk assessment and prevention of cancer. Jun Sun, Bacteria enhance tumorigenesis through activating intestinal stem cells related signaling Pathways
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Last date updated on June, 2014

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