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It has been long-established that cancer and thrombosis are linked, but the exact underlying pathological mechanism remains to be unraveled. As the initiator of the coagulation cascade, the transmembrane glycoprotein tissue factor (TF) has been intensely investigated for its role in cancer-associated thrombosis and cancer progression. TF expression is regulated by both specific oncogenes and environmental factors, and it is shown to regulate primary growth and metastasis formation in a variety of cancer models. In clinical studies, TF has been shown to be overexpressed in most cancer types and is strongly associated with disease progression. While TF clearly associates with cancer progression, a prominent role for TF in the development of cancer-associated thrombosis is less clear. The current concept is that cancer-associated thrombosis is associated with the secretion of tumor-derived TF-positive extracellular vesicles in certain tumor types. To date, many therapeutic strategies to target TF-both in preclinical and clinical phase-are being pursued, including targeting TF or the
FVIIa complex by itself or by exploiting TF as a docking molecule to deliver cytotoxic compounds to the tumor. In this review, the authors summarize the current understanding of the role of TF in both cancer progression and cancer-associated thrombosis, and discuss novel insights on TF as a therapeutic target as well as a biomarker for cancer progression and VTE.
This article was published in the following journal.
Name: Seminars in thrombosis and hemostasis
Tissue factor overexpression is associated with tumor progression, venous thromboembolism, and worsened survival in patients with cancer. Tissue factor and activated factor VII (FVIIa) complex may con...
There is a strong relationship between tissue factor (TF) and cancer. Many cancer cells express high levels of both full-length TF and alternatively spliced (as) TF. TF expression in cancer is associa...
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Tissue factor is the main activator of coagulation cascades. Excessive tissue factor expression is made responsible of thrombosis in a number of clinical situations including thrombosis in...
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A tumor, basically a carcinoma with a single sarcoma such as leiomyosarcoma or angiosarcoma or multiple sarcomas of uterine origin. The role of estrogen has been postulated as a possible etiological factor in this tumor. (Holland et al., Cancer Medicine, 3d ed, p1703)
A secreted tumor necrosis factor receptor family member that has specificity FAS LIGAND and TUMOR NECROSIS FACTOR LIGAND SUPERFAMILY MEMBER 14. It plays a modulating role in tumor necrosis factor signaling pathway.
A tumor necrosis factor receptor subtype with specificity for TUMOR NECROSIS FACTOR LIGAND SUPERFAMILY MEMBER 15. It is found in tissues containing LYMPHOCYTES and may play a role in regulating lymphocyte homeostasis and APOPTOSIS. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
A novel member of the tumor-necrosis factor receptor family that can also mediate HERPES SIMPLEX VIRUS TYPE 1 entry into cells. It has specificity for TUMOR NECROSIS FACTOR LIGAND SUPERFAMILY MEMBER 14 and the homotrimeric form of LYMPHOTOXIN-ALPHA. The receptor is abundantly expressed on T-LYMPHOCYTES and may play a role in regulating lymphocyte activation. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
A widely expressed member of the TNF receptor-associated family that may play a role in neuronal development and EMBRYOGENESIS. Although TNF receptor-associated factor 4 does not strongly associate with TUMOR NECROSIS FACTOR RECEPTORS it may be a signaling partner with the GLUCOCORTICOID-INDUCED TNFR-RELATED PROTEIN that plays a role in the activation of JNK MITOGEN-ACTIVATED PROTEIN KINASES and NF-KAPPA B.
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