Old dogs and new tricks: proteases, inhibitors, and cell migration.

A new model for the actions of plasminogen activator inhibitors (PAIs) on cell migration may resolve the conflicting research data on these proteins in metastasis and angiogenesis. Results from two groups reveal a role for PAI-1 in promoting cycles of attachment and detachment of the cell from the extracellular matrix that is independent of its role as an enzymatic inhibitor of urokinase-type plasminogen activator (uPA). Through the formation of a complex of integrins, uPA and its receptor, and the clearance receptors of the low-density lipoprotein family, PAI-1 may promote endocytosis and recycling of these adhesion-controlling proteins, allowing cycling of cellular attachment and detachment.