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J. Cell Biol.,
Volume 141, Number 2, April 20, 1998 515-526

* Department of Cell and Structural Biology, Integrin receptors play a central role in cell
migration through their roles as adhesive receptors for
both other cells and extracellular matrix components.
In this study, we demonstrate that integrin and cadherin receptors coordinately regulate contact-mediated inhibition of cell migration. In addition to promoting proliferation (Sastry, S., M. Lakonishok, D. Thomas, J. Muschler, and A. Horwitz. 1996. J. Cell
Biol. 133:169-184), ectopic expression of the
Department of Pediatrics, University of Illinois at Urbana-Champaign, Urbana,
Illinois 61801; and § Lankenau Medical Research Center, Wynnewood, Pennsylvania 19096
5 integrin in cultures of primary quail myoblasts promotes a
striking contact-mediated inhibition of cell migration.
Myoblasts ectopically expressing
5 integrin (
5 myoblasts) move normally when not in contact, but upon
contact, they show inhibition of migration and motile
activity (i.e., extension and retraction of membrane
protrusions). As a consequence, these cells tend to
grow in aggregates and do not migrate to close a
wound. This phenotype is also seen with ectopic expression of
1 integrin, paxillin, or activated FAK (CD2
FAK) and therefore appears to result from enhanced
integrin-mediated signaling. The contact inhibition observed in the
5 myoblasts is mediated by N-cadherin,
whose expression is upregulated more than fivefold.
Perturbation studies using low calcium conditions, antibody inhibition, and ectopic expression of wild-type
and mutant N-cadherins all implicate N-cadherin in the
contact inhibition of migration. Ectopic expression of
N-cadherin also produces cells that show inhibited migration upon contact; however, they do not show suppressed motile activity, suggesting that integrins and cadherins coordinately regulate motile activity. These
observations have potential importance to normal and
pathologic processes during embryonic development
and tumor metastasis.
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