Tissue Factor Noncoagulant Signaling: Mechanisms and Implications for Cell Migration and Apoptosis

Semin Thromb Hemost. 2015 Oct;41(7):691-9. doi: 10.1055/s-0035-1564046. Epub 2015 Sep 29.

Abstract

Tissue factor (TF) is a 47-kDa transmembrane glycoprotein and the main initiator of the blood coagulation cascade. Binding to its ligand factor VIIa (FVIIa) also initiates noncoagulant signaling with broad biological implications. In this review, we discuss how TF interacts with other cell-surface proteins, which affect biological functions such as cell migration and cell survival. A vast number of publications have demonstrated the importance of TF-induced activation of protease-activated receptors, but recently published research has indicated a more complicated picture. As it has been discovered that TF interacts with integrins and receptor tyrosine kinases, novel signaling mechanisms for the TF/FVIIa complex have been presented. The knowledge of these new aspects of TF signaling may, for instance, facilitate the development of new treatment strategies for cancer and acute coronary syndromes, two examples of diseases characterized by aberrant TF expression and signaling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acute Coronary Syndrome / metabolism*
  • Acute Coronary Syndrome / pathology
  • Acute Coronary Syndrome / therapy
  • Animals
  • Apoptosis*
  • Cell Movement*
  • Cell Survival
  • Factor VIIa / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Neoplasm Proteins / metabolism*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Protein Binding
  • Signal Transduction*
  • Thromboplastin / metabolism*

Substances

  • Neoplasm Proteins
  • Thromboplastin
  • Factor VIIa