Tissue factor (Coagulation factor III) (TF)

Tissue factor (TF), also known as coagulation factor III or CD142, is a 47-kDa transmembrane glycoprotein that serves as the primary initiator of the extrinsic coagulation cascade (UniProt P13726). Under physiological conditions, TF is sequestered from the blood by the vascular endothelium, but upon injury, it is exposed and binds to circulating Factor VII/VIIa with high affinity (PubMed: 15170404). The resulting TF-FVIIa complex acts as a protease that activates Factor IX and Factor X, ultimately leading to thrombin generation and fibrin formation. Beyond hemostasis, TF plays a critical role in cell signaling through the activation of protease-activated receptors (PARs), which promotes angiogenesis, inflammation, and cell proliferation (PubMed: 22539486). In disease, overexpression of TF is associated with pathological thrombosis, cardiovascular disease, and the progression of various cancers, where it facilitates metastasis and tumor-associated angiogenesis (PubMed: 23133406). Therapeutic targeting of the TF-FVIIa binding site includes the use of monoclonal antibodies and antibody-drug conjugates, such as Tisotumab vedotin, to treat malignancies and thrombotic disorders (DrugBank: DB15578).

Other names

Coagulation factor IIIThromboplastinCD142F3Platelet tissue factor

Inhibition of the TF-FVIIa complex formation to prevent the initiation of the extrinsic coagulation pathway, or targeting TF-expressing cells via antibody-drug conjugates for cytotoxic delivery.