Abstract
The urokinase-type plasminogen activator (uPA) system plays a central role in control of cell surface proteolysis and extracellular matrix degradation. Components of this system are upregulated in a wide variety of human cancers and high levels of these proteins predict more rapid relapse and shorter survival. Recently, additional complexities in this system have been recognised, especially with regard to the roles of plasminogen activator inhibitor-1 (PAI-1), the urokinase receptor (uPAR) and urokinase:uPAR complexes. PAI-1 has been shown to play a major role in the process of pathological angiogenesis. The uPAR is involved as a key player both in proteolysis and cellular adhesion, where it is both an adhesion receptor itself for vitronectin and interacts with and modifies signalling from integrins. In addition, binding of uPA to the receptor can induce intracellular signalling via a number of different pathways, including integrins and G proteins. These new developments lead to a number of novel targets for drug discovery beyond better established enzyme inhibitors and receptor antagonists.
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