Published 10 October 2005. doi:10.1083/jcb.200506152
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 171, Number 1, 153-164
Integrin-dependent actomyosin contraction regulates epithelial cell scattering
Johan de Rooij1,
Andre Kerstens1,
Gaudenz Danuser1,
Martin A. Schwartz2,3, and
Clare M. Waterman-Storer1
1 Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037
2 Department of Microbiology, Cardiovascular Research Center, Mellon Prostate Cancer Institute, University of Virginia, Charlottesville, VA 22908
3 Department of Biomedical Engineering, Cardiovascular Research Center, Mellon Prostate Cancer Institute, University of Virginia, Charlottesville, VA 22908
Correspondence to Johan de Rooij: j.d.rooij{at}nki.nl
The scattering of Madin-Darby canine kidney cells in vitro mimics key aspects of epithelialmesenchymal 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 cellcell junctions. Scattering is enhanced on collagen and fibronectin, as compared with laminin1, suggesting possible cross talk between integrins and cellcell 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 cellcell junctions may disrupt cellcell 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 cellcell adhesion during epithelial cell scattering.
M.A. Schwartz and C.M. Waterman-Storer contributed equally to this paper.
J. de Rooij's present address is Dept. of Cell Biology, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands.
A. Kersten's present address is University of Texas at El Paso, College of Engineering, El Paso, TX 79968.
Abbreviations used in this paper: 2D, two-dimensional; CCD, charge-coupled device; Cn, collagen; EMT, epithelialmesenchymal transition; Fn, fibronectin; HGF, hepatocyte growth factor; Ln, laminin; MLC, myosin II regulatory light chain; Vn, vitronectin; ZO-1, zona-occludens-1.

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