Bacterial activation of β-catenin signaling in human epithelia

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Abstract
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 β-catenin signaling, a key component in regulating epithelial cell proliferation. The nonpathogenic Salmonella strain PhoPc activates the β-catenin signaling pathway of human epithelia via a blockade of β-catenin degradation. Normal β-catenin ubiquitination necessary for constitutive β-catenin degradation is abolished, allowing the accumulation and translocation of β-catenin to the nucleus. Transcriptional activation mediated by the β-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 β-catenin activation. These data suggest that nonvirulent bacterial-epithelial interactions can influence β-catenin signaling and cell growth control in a manner previously unsuspected.