title: N-cadherin-mediated cell-cell adhesion promotes cell migration in a three-dimensional matrix.
abstract: Cancer cells that originate from epithelial tissues typically lose epithelial specific cell-cell junctions, but these transformed cells are not devoid of cell-cell adhesion proteins. Using hepatocyte-growth-factor-treated MDCK cells that underwent a complete epithelial-to-mesenchymal transition, we analyzed cell-cell adhesion between these highly invasive transformed epithelial cells in a three-dimensional (3D) collagen matrix. In a 3D matrix, these transformed cells formed elongated multicellular chains, and migrated faster and more persistently than single cells in isolation. In addition, the cell clusters were enriched with stress-fiber-like actin bundles that provided contractile forces. N-cadherin-knockdown cells failed to form cell-cell junctions or migrate, and the expression of the N-cadherin cytoplasmic or extracellular domain partially rescued the knockdown phenotype. By contrast, the expression of N-cadherin-α-catenin chimera rescued the knockdown phenotype, but individual cells within the cell clusters were less mobile. Together, our findings suggest that a dynamic N-cadherin and actin linkage is required for efficient 3D collective migration.
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, CA 95616,  USA.
authors.forename: Wenting
authors.initials: W
authors.lastname: Shih
authors.forename: Soichiro
authors.initials: S
authors.lastname: Yamada
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology*; D002460:Cell Line; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000502:physiology*; D003094:Collagen / Q000737:chemistry; D003599:Cytoskeleton / Q000378:metabolism; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000502:physiology; D055785:Gene Knockdown Techniques; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D061985:Madin Darby Canine Kidney Cells; D022502:Stress Fibers / Q000378:metabolism; D051178:alpha Catenin / Q000378:metabolism
chemical_list: D000199:Actins; D015820:Cadherins; D051178:alpha Catenin; D017228:Hepatocyte Growth Factor; D003094:Collagen