The interaction between urokinase receptor and vitronectin in cell adhesion and signalling.
The extracellular matrix (ECM) is a complex structural entity surrounding and supporting cells present in all tissue and organs. Cell-matrix interactions play fundamental roles during embryonic development, morphogenesis, tissue homoeostasis, wound healing, and tumourigenesis. Cell-matrix communication is kept in balance by physical contact and by transmembrane integrin receptors providing the dynamic link between the extracellular and intracellular environments through bi-directional signalling. The urokinase-type plasminogen activator receptor (uPAR) is a plasma membrane receptor overexpressed during inflammation and in almost all human cancers. One of its functions is to endorse ECM remodelling through the activation of plasminogen and downstream proteases, including matrix-metalloproteases (MMPs). Beside its role in ECM degradation, uPAR modulates cell-matrix contact through a direct engagement with the ECM component, vitronectin (Vn), and by regulating the activity state of integrins thus promoting or inhibiting integrin signalling and integrin-mediated cell adhesion to other ECM components, like fibronectin and collagen. In this review we have centred our attention on the non-proteolytic function of uPAR as a mediator of cell adhesion and downstream signalling.
Madsen
Chris D
CD
FIRC Institute of Molecular Oncology, Via Adamello, 16, I-20139 Milan, Italy. chris.madsen@ifom-ieo-campus.it
Sidenius
Nicolai
N
D000818:Animals; D002448:Cell Adhesion; D005109:Extracellular Matrix / Q000378:metabolism; D022001:Focal Adhesions; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008954:Models, Biological; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D015398:Signal Transduction; D019096:Vitronectin / Q000378:metabolism*
D016023:Integrins; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D019096:Vitronectin