Tissue factor-integrin interactions in cancer and thrombosis: every Jack has his Jill
Article first published online: 30 JUN 2013
© 2013 International Society on Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis
Special Issue: State of the Art 2013
Volume 11, Issue Supplement s1, pages 285–293, June 2013
How to Cite
Tissue factor-integrin interactions in cancer and thrombosis: every Jack has his Jill. J Thromb Haemost 2013; 11(Suppl. 1): 285–93., .
- Issue published online: 30 JUN 2013
- Article first published online: 30 JUN 2013
- angiogenesis inducers;
- beta integrins;
- blood coagulation factors;
- cell migration;
- protease-activated receptor 2
Tissue factor (TF) is a 47 kDa membrane protein that initiates coagulation by binding to FVII(a) and FX(a) and is a risk factor for thrombosis in many disease states. In addition to its coagulant activity, TF also influences cancer progression by triggering signaling effects via a group of G-protein coupled receptors named protease-activated receptors (PARs). TF localizes to cytoskeletal structures in migrating cells, influences cytoskeleton reorganization and promotes migration. Recently, integrins, important mediators of cell motility, have emerged as important binding partners for TF and influence both TF coagulant and PAR-2-dependent signaling functions. Direct binding of TF to integrins also impacts processes such as cell migration and signaling independent of PAR-2. A recently discovered alternatively spliced, soluble TF isoform also ligates integrins to augment angiogenesis, thus fuelling cancer progression. To date, the literature describes a complex interplay between different integrin subunits and distinct TF isoforms, but our understanding of TF-integrin bidirectional regulation remains clouded. In this review, we aim to summarize the existing knowledge on integrin-TF interaction and speculate on its relevance to physiology and pathology.