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

Chibby1 (Cby1) was originally isolated as a binding partner for β-catenin, a dual function protein in cell-cell adhesion and in canonical Wnt signaling. The canonical Wnt/β-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 β-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.

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