Regulation of tissue factor-factor VIIa expression on cell surfaces: a role for tissue factor-factor VIIa endocytosis

Tissue factor (TF) is the cellular receptor for plasma clotting factor VIIa (FVIIa) and the formation of TF-VIIa complexes on cell surfaces triggers the coagulation cascade. Further, TF-VIIa, either directly or indirectly, influences various biological processes, such as development, inflammation and tumor metastasis. Therefore, a proper regulation of TF-VIIa expression is critical for the maintenance of hemostatic balance and health in general. TF-VIIa functional expression on cell surfaces is regulated primarily by transcriptional regulation of TF gene or by specific plasma inhibitors, particularly tissue factor pathway inhibitor (TFPI). However, a number of other mechanisms that are yet to be well defined also regulate TF-VIIa functional expression. One such mechanism is the endocytosis of TF-VIIa. In this article, we provide a comprehensive review on the regulation of TF-VIIa functional expression by these other mechanisms, with a particular emphasis on TF-VIIa endocytosis, and our perspective of these studies.