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Cellular consequences upon factor VIIa binding to tissue factor
1Department of Medical Sciences, Laboratory for Coagulation Research, University Hospital, Uppsala, Sweden. agneta.siegbahn@klinikem.uas.lul.se
Haemostasis
|March 17, 2001
Summary
Tissue factor (TF) and factor VIIa (FVIIa) activate coagulation. This complex also independently influences cell signaling, impacting angiogenesis, metastasis, and migration.
Area of Science:
- Biochemistry
- Cell Biology
- Oncology
Background:
- Tissue factor (TF) is a glycoprotein crucial for initiating blood coagulation via complex formation with factor VIIa (FVIIa).
- Normally found on extravascular cells, TF can be expressed by monocytes, endothelial cells, and malignant cells.
- TF expression in non-vascular sites and its induction in circulating cells are key areas of research.
Purpose of the Study:
- To elucidate the non-coagulant functions of the FVIIa/TF complex.
- To investigate the mechanisms of intracellular signaling mediated by FVIIa/TF.
- To understand the role of TF in processes like angiogenesis, metastasis, cell adhesion, and migration.
Main Methods:
- Analysis of FVIIa binding to TF on various cell types.
- Investigation of intracellular signaling pathways independent of coagulation cascade activation.
- Examination of TF's role in cellular functions using in vitro models.
Main Results:
- The FVIIa/TF complex mediates intracellular signaling independently of blood coagulation.
- TF influences angiogenesis, cancer metastasis, cell adhesion, and migration.
- Signaling occurs through at least two distinct mechanisms: one protease-dependent and one cytoplasmic domain-dependent.
Conclusions:
- The FVIIa/TF complex possesses significant biological functions beyond coagulation initiation.
- TF-mediated intracellular signaling plays a critical role in cancer progression and cellular dynamics.
- Targeting TF signaling pathways may offer novel therapeutic strategies for cancer and other diseases.