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 …

[1]  N. Lemoine,et al.  Enhanced expression of urokinase receptor induced through the tissue factor-factor VIIa pathway in human pancreatic cancer. , 1998, Cancer research.

[2]  S. L. Gonias,et al.  Binding of Urokinase-type Plasminogen Activator to Its Receptor in MCF-7 Cells Activates Extracellular Signal-regulated Kinase 1 and 2 Which Is Required for Increased Cellular Motility* , 1998, The Journal of Biological Chemistry.

[3]  O. Mayboroda,et al.  The Jak/Stat Pathway and Urokinase Receptor Signaling in Human Aortic Vascular Smooth Muscle Cells* , 1998, The Journal of Biological Chemistry.

[4]  M. Shuman,et al.  Inhibition of prostate cancer neovascularization and growth by urokinase-plasminogen activator receptor blockade. , 1997, Cancer research.

[5]  Y. Wei,et al.  Plasmin and plasminogen activator inhibitor type 1 promote cellular motility by regulating the interaction between the urokinase receptor and vitronectin. , 1997, The Journal of clinical investigation.

[6]  Y. Kook,et al.  Co‐expression of urokinase‐type plasminogen activator and its receptor in human gastric‐cancer cell lines correlates with their invasiveness and tumorigenicity , 1997, International journal of cancer.

[7]  E. Lengyel,et al.  Elevated urokinase-type plasminogen activator receptor expression in a colon cancer cell line is due to a constitutively activated extracellular signal-regulated kinase-1-dependent signaling cascade , 1997, Oncogene.

[8]  L. Ossowski,et al.  Reduction in Surface Urokinase Receptor Forces Malignant Cells into a Protracted State of Dormancy , 1997, The Journal of cell biology.

[9]  J. Foidart,et al.  Involvement of PA/plasmin system in the processing of pro‐MMP‐9 and in the second step of pro‐MMP‐2 activation , 1997, FEBS letters.

[10]  H. Sato,et al.  Proteolytic activation of the precursor of membrane type 1 matrix metalloproteinase by human plasmin , 1997, FEBS letters.

[11]  H. Friess,et al.  Enhanced expression of urokinase plasminogen activator and its receptor in pancreatic carcinoma. , 1997, British Journal of Cancer.

[12]  Michael V. Doyle,et al.  Regulation of Integrin Function by the Urokinase Receptor , 1996, Science.

[13]  F. Blasi,et al.  Proteolytic cleavage of the urokinase receptor substitutes for the agonist‐induced chemotactic effect. , 1996, The EMBO journal.

[14]  J. Otte,et al.  Differential regulation of plasminogen activator and inhibitor gene transcription by the tumor suppressor p53. , 1995, Nucleic acids research.

[15]  J. Skibber,et al.  Transcriptional activation of the urokinase receptor gene in invasive colon cancer , 1994, International journal of cancer.

[16]  H. Verspaget,et al.  Urokinase receptor and colorectal cancer survival , 1994, The Lancet.

[17]  S. Waxman,et al.  Induction of cell migration by pro-urokinase binding to its receptor: possible mechanism for signal transduction in human epithelial cells , 1994, The Journal of cell biology.