Tissue factor isoforms in cancer and blood coagulation

Kocatürk, B. (2015)

Doctoral Thesis

Tissue Factor (TF) is a membrane protein that is responsible for the initiation of the coagulation. In addition to its coagulant activity, it can also signal through a member of G-protein coupled receptor family, PARs, thus play a role in breast cancer growth and angiogenesis. The switch between signaling and coagulant TF regulated by the oxidation/reduction of an allosteric disulfide bond which resides in TF antigen. A decade ago, it was discovered that TF RNA can be alternatively spliced to form a soluble protein called Alternatively Spliced Tissue Factor (asTF). This protein is non-coagulant. However, it plays a major role in breast cancer growth via inducing cancer cell proliferation. The mechanism lying behind behind this phenomenon is asTF's capability to ligate integrins thus it can initiate integrin signaling. Moreover, both TF and asTF can synergize with estrogen pathway thus providing a complex regulation of breast cancer progression.

• Estrogen signaling
• Angiogenesis
• Breast cancer
• Cell proliferation
• Tissue factor
• Coagulation

• All authors: Kocatürk, B.
• Supervisor: Reitsma, P.H.
• Co-supervisor: Versteeg, H.H.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden University Medical Center (LUMC), Leiden University
• Date: 2015-04-29
• ISBN (print): 9789462951273