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

ABSTRACTChibby1 (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- cateninpathway 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 (KD) SW480 colon cancer cells. Unexpectedly, we found that Cby1 KD induces mesenchymal-to-epithelial transition (MET)-like changes in SW480 as well as in HEK293 cells. Cby1-KD cells displayed a cuboidalepithelial morphology with tight cell-cell contacts. In Cby1-KD cells, the plasma membrane localization of E-cadherin and β- cateninwas 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-KD cells exhibited epithelial cell-like properties as they migrated collectively as epithelial sh...