Tissue factor-integrin interactions in cancer and thrombosis: every Jack has his Jill


Kocaturk B., Versteeg H. H.

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, vol.11, pp.285-293, 2013 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Review
  • Volume: 11
  • Publication Date: 2013
  • Doi Number: 10.1111/jth.12222
  • Journal Name: JOURNAL OF THROMBOSIS AND HAEMOSTASIS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.285-293
  • Keywords: angiogenesis inducers, beta integrins, blood coagulation factors, cell migration, protease-activated receptor 2, FACTOR CYTOPLASMIC DOMAIN, CELL-DERIVED MICROPARTICLES, FACTOR EXPRESSION, PANCREATIC-CANCER, TUMOR-GROWTH, FACTOR VIIA, P-SELECTIN, INDEPENDENT MECHANISMS, MICROVESSEL FORMATION, ALLOSTERIC DISULFIDE
  • Hacettepe University Affiliated: Yes

Abstract

Tissue factor (TF) is a 47kDa 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.