Urokinase Receptor - Physiological Significance

Physiological Significance

uPAR is a part of the plasminogen activation system, which in the healthy body is involved in tissue reorganization events such as mammary gland involution and wound healing. In order to be able to reorganize tissue it is important, that the old tissue can be degraded. An important mechanism in this degradation is the proteolysis cascade initiated by the plasminogen activation system. uPAR binds urokinase and thus restricts plasminogen activation to the immediate vicinity of the cell membrane. Thus uPAR seems to be an important player in the regulation of this process.

However the components of the plasminogen activation system have been found to be highly expressed in many malignant tumors, indicating that tumors are able to hijack the system, and use it in metastasis. Thus inhibitors of the various components of the plasminogen activation system has been sought as possible anticancer drugs.

uPAR has been involved in various other non-proteolytical processes related to cancer, such as cell migration, cell cycle regulation and cell adhesion.

When uPA is bound to the receptor, there is cleavage between the GPI-anchor and the uPAR, releasing suPAR.