Beyond thrombosis: the impact of tissue factor signaling in cancer

• Published in: Journal of hematology and oncology Vol. 13; no. 1; pp. 93 - 14
• Main Authors: Unruh, Dusten, Horbinski, Craig
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 14.07.2020; BioMed Central; BMC
• Subjects: Adapter proteins; Amino Acid Sequence; Angiogenesis; Binding sites; Blood platelets; Cancer; Cell Hypoxia; Cell proliferation; Coagulation factors; Cytokines; Factor VII; Factor VIIa - physiology; G protein-coupled receptors; G proteins; Gene Expression Regulation, Neoplastic; Glycoproteins; Hematology; Hemostasis; Humans; Immunotherapy, Adoptive; Integrins; Integrins - metabolism; Kinases; Ligands; Metastases; Metastasis; Molecular Sequence Data; Molecular Targeted Therapy; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins - antagonists & inhibitors; Neoplasm Proteins - physiology; Neoplasms - blood; Neoplasms - blood supply; Neoplasms - physiopathology; Neoplasms - therapy; Neoplastic Stem Cells - pathology; Neovascularization, Pathologic - physiopathology; Oncology; Phosphorylation; Protease-activated receptors; Proteases; Protein Conformation; Protein Domains; Protein Isoforms - physiology; Receptor Protein-Tyrosine Kinases - metabolism; Receptor tyrosine kinases; Receptors, Proteinase-Activated - metabolism; Review; Signal Transduction - physiology; Thromboembolism; Thrombophilia - blood; Thrombophilia - etiology; Thromboplastin - antagonists & inhibitors; Thromboplastin - physiology; Thrombosis; Tissue factor; Tumors; Tyrosine; Wound healing; Angiogenesis; Metastasis; Receptor tyrosine kinases; Tissue factor; Integrins; Protease-activated receptors
• ISSN: 1756-8722; 1756-8722
• DOI: 10.1186/s13045-020-00932-z

Tissue factor (TF) is the primary initiator of the coagulation cascade, though its effects extend well beyond hemostasis. When TF binds to Factor VII, the resulting TF:FVIIa complex can proteolytically cleave transmembrane G protein-coupled protease-activated receptors (PARs). In addition to activating PARs, TF:FVIIa complex can also activate receptor tyrosine kinases (RTKs) and integrins. These signaling pathways are utilized by tumors to increase cell proliferation, angiogenesis, metastasis, and cancer stem-like cell maintenance. Herein, we review in detail the regulation of TF expression, mechanisms of TF signaling, their pathological consequences, and how it is being targeted in experimental cancer therapeutics.