title: Chibby1 knockdown promotes mesenchymal-to-epithelial transition-like changes.
abstract: 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 (KD) SW480 colon cancer cells. Unexpectedly, we found that Cby1 KDinduces mesenchymal-to-epithelial transition (MET)-like changes in SW480 as well as in HEK293 cells. Cby1-KDcells displayed a cuboidal epithelial morphology with tight cell-cell contacts. In Cby1-KDcells, 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-KDcells exhibited epithelial cell-like properties as they migrated collectively as epithelial sheets. Furthermore, the anchorage-independent growth of Cby1-KDcells was reduced as determined by soft agar assays. These findings suggest that chronic Cby1 KDin colon cancer cells may counteract tumor progression by promoting the MET process.
authors.affiliation: a Graduate Program in Molecular and Cellular Pharmacology, Stony Brook University , Stony Brook , NY , USA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Fischer
authors.affiliation: b Department of Pharmacological Sciences , Stony Brook University , Stony Brook , NY , USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Wong
authors.affiliation: a Graduate Program in Molecular and Cellular Pharmacology, Stony Brook University , Stony Brook , NY , USA.|b Department of Pharmacological Sciences , Stony Brook University , Stony Brook , NY , USA.
authors.forename: Feng-Qian
authors.initials: FQ
authors.lastname: Li
authors.affiliation: a Graduate Program in Molecular and Cellular Pharmacology, Stony Brook University , Stony Brook , NY , USA.|b Department of Pharmacological Sciences , Stony Brook University , Stony Brook , NY , USA.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Takemaru
mesh_terms: D015820:Cadherins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D048430:Cell Shape; D004847:Epithelial Cells / Q000378:metabolism; D004848:Epithelium / Q000473:pathology*; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D008648:Mesoderm / Q000473:pathology*; D009687:Nuclear Proteins / Q000378:metabolism*; D021381:Protein Transport; D014945:Wound Healing; D051176:beta Catenin / Q000378:metabolism
chemical_list: C473750:CBY1 protein, human; D015820:Cadherins; D002352:Carrier Proteins; D009687:Nuclear Proteins; D051176:beta Catenin
keywords: Chibby; Chibby1; E-cadherin; cell-cell adhesion; colon cancer; epithelial-to-mesenchymal transition; metastasis; wnt; β-catenin