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Department of Cell Biology, The Scripps Research Institute, La Jolla, California, 92037
To whom requests for reprints should be addressed at 1 The Scripps Research Institute, 10550 N. Torrey Pines Road, VB-3, La Jolla, CA 92037. E-mail: loskutof{at}scrip-ps.edu
Plasminogen activator inhibitor 1 (PAI-1) is the primary physiological inhibitor of plasminogen activation in vivo, and thus it is one of the main regulators of the fibrinolytic system. In this regard, individuals with elevated PAI-1 seem to have an increased risk for thrombotic disease, whereas those lacking the inhibitor develop a lifelong bleeding diathesis. Unexpectedly, recent observations demonstrate that cancer patients with high PAI-1 levels have a poor prognosis for survival. This correlation with metastatic disease may be related to the observation that high PAI-1 levels decrease the adhesive strength of cells for their substratum, and that this de-adhesive activity of PAI-1 is not related to its role as a protease inhibitor. Initial insights into potential mechanisms by which PAI-1 regulates the attachment, detachment, and migration of cells are addressed in this review.
Key Words: plasminogen activator inhibitor 1 • vitronectin • extracellular matrix • cell attachment • cell detachment
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