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Am J Physiol Gastrointest Liver Physiol (February 5, 2004). doi:10.1152/ajpgi.00498.2003
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Submitted on November 25, 2003
Accepted on January 30, 2004

Bacterial activation of {beta}-catenin signaling in human epithelia

Jun Sun1*, Michael E. Hobert1, Anjali S. Rao1, Andrew S. Neish2, and James L. Madara1

1 Department of Pathology, University of Chicago, Chicago, IL, USA
2 Epithelial Pathology Unit, Department of Pathology and Laboratory Medicine, Emory University, School of Medicine, Atlanta, GA, USA

* To whom correspondence should be addressed. E-mail: jsun{at}bsd.uchicago.edu.

The mucosal lining of the human intestine is constantly bathed in a milieu of commensal gut flora, the vast majority of these being non-pathogenic microorganisms. Here, we demonstrate that microbial-epithelial cell interactions not only affect pro-inflammatory pathways, but also influence {beta}-catenin signaling, a key component in regulating epithelial cell proliferation. The non-pathogenic Salmonella strain, PhoPc, 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/TCF 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 non-virulent bacterial-epithelial interactions can influence {beta}-catenin signaling and cell growth control in a previously unsuspected manner.




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