N-cadherin-mediated cell-cell adhesion promotes cell migration in a three-dimensional matrix

Wenting Shih, Soichiro Yamada

Research output: Contribution to journalArticle

72 Scopus citations

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-tomesenchymal transition, we analyzed cell-cell adhesion between these highly invasive transformed epithelial cells in a threedimensional (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 Ncadherin 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.

Original languageEnglish (US)
Pages (from-to)3661-3670
Number of pages10
JournalJournal of Cell Science
Volume125
Issue number15
DOIs
StatePublished - Aug 1 2012

Keywords

  • 3D matrix
  • Cell migration
  • Cell-cell adhesion
  • EMT
  • N-cadherin

ASJC Scopus subject areas

  • Cell Biology

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