Submitted on November 25, 2003
Accepted on January 30, 2004
Bacterial activation of 
-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 
-catenin signaling, a key
component in regulating epithelial cell proliferation. The non-pathogenic Salmonella
strain, PhoPc, 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/TCF 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 non-virulent bacterial-epithelial
interactions can influence -catenin signaling and cell growth control in a previously
unsuspected manner.
