[Frontiers in Bioscience S3, 1500-1510, June 1, 2011]

Tissue Factor signaling: a multi-faceted function in biological processes

Lisa G. van den Hengel, Henri H. Versteeg

The Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands


1. Abstract
2. Introduction
3. PARs
4. Potential mechanisms underlying TF signaling
4.1. Calcium signaling
4.2. Gene expression
4.3. Apoptosis
4.4. Migration
4.5. PAR-independent signaling
4.6. Regulation of TF signaling
5. TF signaling in physiological processes
6. TF signaling in cancer-related events
7. TF signaling in inflammatory events
8. Future perspectives
9. Acknowledgment
10. References


Tissue factor (TF), originally discovered to initiate coagulation, is more recently recognized to be involved in other biological processes, such as migration and anti-apoptosis. TF-mediated signaling regulates gene expression and protein synthesis, leading to alterations in cellular behavior. The proteolytic activity of factor VIIa (FVIIa), beta-1 integrin interaction and protease-activated receptor (PAR) activation are some of the key events involved in TF signaling. Post-translational modifications of TF may regulate signaling but this remains elusive. In vivo studies have established that TF signaling severely contributes to processes like angiogenesis, cancer growth and inflammation. This review focuses on the mechanism underlying TF-mediated intracellular signaling with its related physiological and mainly pathological consequences.