title: Urokinase type plasminogen activator receptor (uPAR) as a new therapeutic target in cancer.
abstract: The urokinase (uPA)-type plasminogen activator receptor (uPAR) is a GPI-anchored receptor that focuses urokinase (uPA) proteolytic activity on the cell surface. uPAR also regulates cell adhesion, migration and proliferation, protects from apoptosis and contributes to epithelial mesenchymal transition (EMT), independently of uPA enzymatic activity. Indeed, uPAR interacts with beta1, beta2 and beta3 integrins, thus regulating their activities. uPAR cross-talks with receptor tyrosine kinases through integrins and regulates cancer cell dormancy, proliferation and angiogenesis. Moreover, uPAR mediates uPA-dependent cell migration and chemotaxis induced by fMet-Leu-Phe (fMLF), through its association with fMLF-receptors (fMLF-Rs). Further, uPAR is an adhesion receptor because it binds vitronectin (VN), a component of provisional extracellular matrix. High uPAR expression predicts for more aggressive disease in several cancer types for its ability to increase invasion and metastasis. In fact, uPAR has been hypothesized to be the link between tumor cell dormancy and proliferation that usually precedes the onset of metastasis. Thus, inhibiting uPAR could be a feasible approach to affect tumor growth and metastasis. Here, we review the more recent advances in the development of uPAR-targeted anti-cancer therapeutic agents suitable for further optimization or ready for the evaluation in early clinical trials.
authors.affiliation: Department of Translational Medical Sciences, University Federico II, Naples, Italy.
authors.forename: Nunzia
authors.initials: N
authors.lastname: Montuori
authors.affiliation: Department of Translational Medical Sciences, University Federico II, Naples, Italy.
authors.forename: Ada
authors.initials: A
authors.lastname: Pesapane
authors.affiliation: Department of Translational Medical Sciences, University Federico II, Naples, Italy.
authors.forename: Francesca W
authors.initials: FW
authors.lastname: Rossi
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Salerno, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Giudice
authors.affiliation: Department of Translational Medical Sciences, University Federico II, Naples, Italy.
authors.forename: Amato
authors.initials: A
authors.lastname: De Paulis
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Salerno, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Selleri
authors.affiliation: Department of Chemistry and Biology, University of Salerno, Salerno, Italy.
authors.forename: Pia
authors.initials: P
authors.lastname: Ragno
keywords: metastasis; monoclonal antibody; plasminogen activation; small molecules; uPAR