Bacterial activation of -catenin signaling in human epithelia

Sun, Jun, Michael E. Hobert, Anjali S. Rao, Andrew S. Neish, and James L. Madara. Bacterial activation of -catenin signaling in human epithelia. Am J Physiol Gastrointest Liver Physiol 287: G220– G227, 2004. First published February 5, 2004; 10.1152/ajpgi.00498. 2003.—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 -catenin signaling, a key component in regulating epithelial cell proliferation. The nonpathogenic Salmonella strain PhoP activates the -catenin signaling pathway of human epithelia via a blockade of -catenin degradation. Normal -catenin ubiquitination necessary for constitutive -catenin degradation is abolished, allowing the accumulation and translocation of -catenin to the nucleus. Transcriptional activation mediated by the -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 -catenin activation. These data suggest that nonvirulent bacterial-epithelial interactions can influence -catenin signaling and cell growth control in a manner previously unsuspected.