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First published online 29 April 2008
doi: 10.1242/jcs.020149


Journal of Cell Science 121, 1661-1670 (2008)
Published by The Company of Biologists 2008
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Research Article

PAI1 stimulates assembly of the fibronectin matrix in osteosarcoma cells through crosstalk between the {alpha}vβ5 and {alpha}5β1 integrins

Daniel Vial and Paula J. McKeown-Longo*

Center for Cell Biology and Cancer Research (MC-165), Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USA

* Author for correspondence (e-mail: mckeowp{at}mail.amc.edu)

Accepted 27 February 2008

The plasminogen activation system regulates matrix remodeling through both proteolytic and non-proteolytic mechanisms. Studies were undertaken to determine the effects of the plasminogen activator inhibitor 1 (PAI1) on the assembly of the fibronectin matrix. The addition of PAI1 to MG-63 cells caused a 1.5- to threefold increase in the rate of fibronectin matrix assembly which was associated with an increase in β integrin activation. PAI1 treatment led to a marked decrease in focal contacts and stress fibers, whereas tensin-containing matrix contacts remained unaffected. The effects of PAI1 on matrix assembly were independent of both urokinase-type plasminogen activator (uPA) and urokinase-type plasminogen activator receptor (uPAR), indicating that the stimulation of matrix assembly by PAI1 does not depend on its anti-proteolytic activity or on the association of uPAR with integrin receptors. Antagonists of the {alpha}vβ5 integrin mimicked the effect of PAI1 on cell morphology and fibronectin matrix deposition, indicating that stimulation of matrix assembly by PAI1 required disruption of the interaction between the {alpha}vβ5 integrin and vitronectin. Consistent with this conclusion, the Q123K PAI1 mutant which does not bind vitronectin had no effect on matrix assembly. Our data identify PAI1 as a novel regulator of fibronectin matrix assembly, and indicate that this regulation occurs through a previously undescribed crosstalk between the {alpha}vβ5 and {alpha}5β1 integrins.

Key words: PAI1, Integrin, Fibronectin, Extracellular matrix, Actin


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