Figure 2.

Activation of protease-activated receptors is a major mechanism of tissue factor-coagulation factor VIIa signaling in breast cancer cells. The proteolytic activities of the TF-fVIIa binary complex [potentially (designated as dotted line) ternary complex with fXa] cleave the N-terminal end of PARs. PARs are then activated via intra-molecular binding between the newly created N-terminus and an extracellular loop region of the receptors. Activation of these G-protein-coupled receptors subsequently activates downstream signaling cascades. A number of studies have indicated that PAR2 is crucial for activation of a TF-fVII-driven signaling cascade in breast cancer cells. The role of TF-fVII on PAR1 signaling in breast cancer cells is less evident. FVII: Coagulation factor VII; TF: Tissue factor; PARs: Protease-activated receptors.