Published 13 October 2003. doi:10.1083/jcb1632iti4
© The Rockefeller University Press,
0021-9525/2003/10/11 $8.00
The Journal of Cell Biology, Volume 163, Number 1, 11-11
Integrin is on uPAR to unleash cells
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E-cadherin (green) contacts dissolve when uPAR and  3ß1 interact (right).
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On page 177, Zhang et al. show that the extracellular domain of the 3ß1 integrin can hijack a glycolipid- anchored receptor and thus trigger movement of an epithelial cell by inhibiting E-cadherin–mediated cell contacts.
Integrins on epithelial cells are well known to tether the cells to matrix components—laminin-5 in the case of 3ß1—but are not usually associated with cell–cell contacts. Zhang et al. show that 3ß1 can inhibit cell–cell contacts when 3 binds to the urokinase receptor, uPAR, a known inducer of cell migration in response to certain cytokines. Expression of both uPAR and 3ß1 mobilized cells by reducing E-cadherin and 
-catenin levels at cell junctions, thus dissociating the cells. Other uPAR-induced changes included expression of several genes that are associated with the epithelial–mesenchymal transition, such as the transcription factor SLUG.
The mesenchymal phenotype is a result of localized Src kinase activation induced by the uPAR–3ß1 complex. Disruption of Src signaling by overexpression of its protein interaction domains inhibited uPAR-induced cell motility. High uPAR levels are associated with tumor metastasis and a poor prognosis. Since mutations in the 3 extracellular domain that abolish uPAR binding also block motility, mice expressing these mutants may have a better prognosis. 
Nicole LeBrasseur
lebrasn{at}rockefeller.edu
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