Integrin-dependent actomyosin contraction regulates epithelial cell scattering.
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.
de Rooij
Johan
J
Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Kerstens
Andre
A
Danuser
Gaudenz
G
Schwartz
Martin A
MA
Waterman-Storer
Clare M
CM
D000205:Actomyosin / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000502:physiology; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004285:Dogs; D015536:Down-Regulation; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D016023:Integrins / Q000502:physiology*; D007365:Intercellular Junctions / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D024462:Myosin Type II / Q000502:physiology
D015820:Cadherins; D016023:Integrins; D017228:Hepatocyte Growth Factor; D000205:Actomyosin; D024462:Myosin Type II