Affiliation:
1. Department of Biomedical Engineering, University of California, Davis, CA 95616, USA
Abstract
Summary
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.
Publisher
The Company of Biologists
Cited by
108 articles.
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