Abstract
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.
Keywords:
Angiogenesis; Integrins; Metastasis; Protease-activated receptors; Receptor tyrosine kinases; Tissue factor.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Amino Acid Sequence
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Cell Hypoxia
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Factor VIIa / physiology
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Gene Expression Regulation, Neoplastic
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Humans
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Immunotherapy, Adoptive
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Integrins / metabolism
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Molecular Sequence Data
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Molecular Targeted Therapy
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Neoplasm Invasiveness
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Neoplasm Metastasis
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Neoplasm Proteins / antagonists & inhibitors
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Neoplasm Proteins / physiology*
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Neoplasms / blood supply
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Neoplasms / blood*
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Neoplasms / physiopathology
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Neoplasms / therapy
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Neoplastic Stem Cells / pathology
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Neovascularization, Pathologic / physiopathology
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Protein Conformation
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Protein Domains
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Protein Isoforms / physiology
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Receptor Protein-Tyrosine Kinases / metabolism
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Receptors, Proteinase-Activated / metabolism
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Signal Transduction / physiology
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Thrombophilia / blood*
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Thrombophilia / etiology
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Thromboplastin / antagonists & inhibitors
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Thromboplastin / physiology*
Substances
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Integrins
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Neoplasm Proteins
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Protein Isoforms
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Receptors, Proteinase-Activated
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Thromboplastin
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Receptor Protein-Tyrosine Kinases
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Factor VIIa