Fig. 4. PARs function in the vasculature and in tumor invasion and metastasis. PAR function is shown in the context of a blood vessel. Thrombin, the main effector protease of the coagulation cascade, activates PAR1, PAR3 and PAR4 to elicit signalling in a variety of cell types. Thrombin activates PAR1 and PAR4 in human platelets and generates fibrin, which is important for thrombus formation and tumor cell survival and metastasis. FXa can also cleave and activate PAR1. Activated endothelial cells express tissue factor (TF) and are represented by an oval shape. PAR2 is activated by TF-bound FVIIa and FXa but not by thrombin. PAR1 and PAR2 are also cleaved and activated by tumor-generated proteases, which contribute to tumor cell growth, invasion and metastasis.