Bacterial activation of beta-catenin signaling in human epithelia.

The mucosal lining of the human intestine is constantly bathed in a milieu of commensal gut flora, the vast majority of these being nonpathogenic microorganisms. Here, we demonstrate that microbial-epithelial cell interactions not only affect proinflammatory pathways but also influence beta-catenin signaling, a key component in regulating epithelial cell proliferation. The nonpathogenic Salmonella strain PhoP(c) activates the beta-catenin signaling pathway of human epithelia via a blockade of beta-catenin degradation. Normal beta-catenin ubiquitination necessary for constitutive beta-catenin degradation is abolished, allowing the accumulation and translocation of beta-catenin to the nucleus. Transcriptional activation mediated by the beta-catenin/T cell factor complex increases c-myc expression and enhances cell proliferation. We also show that the Salmonella effector protein AvrA is involved in modulating this beta-catenin activation. These data suggest that nonvirulent bacterial-epithelial interactions can influence beta-catenin signaling and cell growth control in a manner previously unsuspected.