The Urokinase Receptor and Integrins Constitute a Cell Migration Signalosome
Initially identified as a permissive receptor involved in the regulation of pericellular proteolysis, the receptor of urokinase, urokinase-type plasminogen activator receptor (uPAR), is also a signaling receptor capable of regulating tissue remodeling, cell adhesion, differentiation, proliferation, and migration. Therefore, the uPA/uPAR system can permit a tumor cell to modify its environment or to move across it. uPAR exerts these effects by interacting laterally with other membrane receptors such as seven-transmembrane domain receptors, tyrosine kinase receptors, and integrins. This latter family of receptors mediates bidirectional signaling and is connected to the cell cytoskeleton. Beside their well-documented roles in cell adhesion and migration, integrins promote cell survival and resistance to genotoxic injury, crucial properties that allow a tumor cell to adapt to new environments and survive in hostile conditions. Therefore, combining the uPA/uPAR system to the integrin system provides an ultimate advantage to the tumoral cell. Moreover, thanks to the large array of ligands and membrane-bound partners, formation of the uPAR-integrin complex represents the cornerstone that consents to build up larger signaling complexes and to adjust their compositions in order to satisfy the various cellular/tumoral requirements as the tumor cells grow, invade, or disseminate. Therefore, the uPAR-integrin complexes constitute convenient adaptable signaling complexes, some kind of “chameleon signalosome.” This chapter will discuss these issues, describing the influence of uPAR on integrin activity (and conversely) and signaling, and summarize our understanding of the molecular basis of uPAR-integrin interactions. In addition, new challenging data that may revolutionize the classical view of uPAR-integrin interaction will be also discussed.
KeywordsCell Migration Lipid Raft Urokinase Receptor High Molecular Weight Kininogen uPAR Expression
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