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Unexpected role of plasminogen activator inhibitor 1 in cell adhesion and detachment

Ralf-Peter Czekay1, David J Loskutoff

  • 1Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Experimental Biology and Medicine (Maywood, N.J.)
|November 27, 2004
PubMed

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.

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