Molecular interactions involving urokinase plasminogen activator (uPA), its receptor (uPAR) and its inhibitor, plasminogen activator inhibitor-1 (PAI-1), as new targets for tumour therapy

in Expert Opinion on Therapeutic Targets (1999), 3(3), 469-48113

In the promotion of cancer progression, a classical role had previously been ascribed to the plasminogen activation system on the basis of urokinase plasminogen activator (uPA) proteolytic activity and ... [more ▼]

In the promotion of cancer progression, a classical role had previously been ascribed to the plasminogen activation system on the basis of urokinase plasminogen activator (uPA) proteolytic activity and plasminogen activation triggering a focalised pericellular activation cascade involving matrix metalloproteinases (MMPs). As a result, many pharmaceutical companies have undertaken the development of synthetic uPA inhibitors. However, during the last few years, data have accumulated that uPA, as well as urokinase-type plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1), are likely to play an essential role in tumour progression through non-proteolysis-related activities. Such activities endow them with new and likely key functions in tumour progression-associated events, such as cellular adhesion, migration, invasion and angiogenesis. Since these activities essentially depend upon protein-protein interactions, they represent new therapeutic targets. [less ▲]