Urokinase receptor is a key player in tumour progression

See article on page 798 Cell–cell and cell–extracellular matrix (ECM) interactions are essential for cell migration, tissue remodelling, angiogenesis, and tumorigenesis. Pericellular proteolysis of cell surface molecules and ECM provides crucial information in the local environment. Urokinase (uPA) plays an important role through the activation of plasminogen to plasmin, which regulates degradation of elements within the ECM, such as fibrin, fibronectin and lamin, and proteolytic activation of growth factors including hepatocyte growth factor (HGF), basic fibroblast growth factor (FGF-2) and transforming growth factor β (TGF-β). Plasmin also activates the proenzyme forms of the matrix metalloproteinases (MMPs), such as MT1-MMP,1MMP-2 and MMP-9.2 uPA activation is regulated by its specific cell surface receptor, urokinase receptor (uPAR). Binding of uPA to its receptor (uPAR) accelerates uPA activation from an inactive proenzyme (pro-uPA). The activity of plasminogen activators can be regulated by the specific inhibitors, plasminogen activator inhibitor 1 (PAI-1) and plasminogen activator inhibitor 2 (PAI-2). The urokinase system is implicated in tumour cell invasion on a basis of generally increased uPA activity in metastatic tumours. In particular, uPAR expression on the surface …