Integrin-dependent actomyosin contraction regulates epithelial cell scattering

J Cell Biol. 2005 Oct 10;171(1):153-64. doi: 10.1083/jcb.200506152.

Abstract

The scattering of Madin-Darby canine kidney cells in vitro mimics key aspects of epithelial-mesenchymal transitions during development, carcinoma cell invasion, and metastasis. Scattering is induced by hepatocyte growth factor (HGF) and is thought to involve disruption of cadherin-dependent cell-cell junctions. Scattering is enhanced on collagen and fibronectin, as compared with laminin1, suggesting possible cross talk between integrins and cell-cell junctions. We show that HGF does not trigger any detectable decrease in E-cadherin function, but increases integrin-mediated adhesion. Time-lapse imaging suggests that tension on cell-cell junctions may disrupt cell-cell adhesion. Varying the density and type of extracellular matrix proteins shows that scattering correlates with stronger integrin adhesion and increased phosphorylation of the myosin regulatory light chain. To directly test the role of integrin-dependent traction forces, substrate compliance was varied. Rigid substrates that produce high traction forces promoted scattering, in comparison to more compliant substrates. We conclude that integrin-dependent actomyosin traction force mediates the disruption of cell-cell adhesion during epithelial cell scattering.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actomyosin / metabolism*
  • Animals
  • Cadherins / physiology
  • Cell Adhesion
  • Cell Line
  • Cell Movement / drug effects
  • Cell Movement / physiology*
  • Cells, Cultured
  • Dogs
  • Down-Regulation
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelial Cells / physiology*
  • Extracellular Matrix / physiology
  • Hepatocyte Growth Factor / pharmacology
  • Integrins / physiology*
  • Intercellular Junctions / metabolism
  • Kidney / cytology
  • Kidney / metabolism
  • Myosin Type II / physiology

Substances

  • Cadherins
  • Integrins
  • Hepatocyte Growth Factor
  • Actomyosin
  • Myosin Type II