Chibby1 knockdown promotes mesenchymal-to-epithelial transition-like changes

Chibby1 (Cby1) was originally isolated as a binding partner for -catenin, a dual function protein in cell-cell adhesion and in canonical Wnt signaling. The canonical Wnt/-catenin pathway is dysregulated in various diseases including cancer, most notably of the gastrointestinal origin. To investigate the role of Cby1 in colorectal tumorigenesis, we generated stable Cby1-knockdown (K-D) SW480 colon cancer cells. Unexpectedly, we found that Cby1 K-D induces mesenchymal-to-epithelial transition (MET)-like changes in SW480 as well as in HEK293 cells. Cby1-K-D cells displayed a cuboidal epithelial morphology with tight cell-cell contacts. In Cby1-K-D cells, the plasma membrane localization of E-cadherin and -catenin was dramatically increased with formation of cortical actin rings, while the levels of the mesenchymal marker vimentin were decreased. Consistent with these changes, in wound healing assays, Cby1-K-D cells exhibited epithelial cell-like properties as they migrated collectively as epithelial sheets. Furthermore, the anchorage-independent growth of Cby1-K-D cells was reduced as determined by soft agar assays. These findings suggest that chronic Cby1 K-D in colon cancer cells may counteract tumor progression by promoting the MET process.