Tissue factor: a neglected role in cancer biology.

Tissue factor (TF), an initiator of extrinsic coagulation pathway, is positively correlated with venous thromboembolism (VTE) of tumor patients. Beyond thrombosis, TF plays a vital role in tumor progression. TF is highly expressed in cancer tissues and circulating tumor cell (CTC), and activates factor VIIa (FVIIa), which increases tumor cells proliferation, angiogenesis, epithelial-mesenchymal transition (EMT) and cancer stem cells(CSCs) activity. Furthermore, TF and TF-positive microvesicles (TF+MVs) activate the coagulation system to promote the clots formation with non-tumor cell components (e.g., platelets, leukocytes, fibrin), which makes tumor cells adhere to clots to form CTC clusters. Then, tumor cells utilize clots to cause its reducing fluid shear stress (FSS), anoikis resistance, immune escape, adhesion, extravasation and colonization. Herein, we review in detail that how TF signaling promotes tumor metastasis, and how TF-targeted therapeutic strategies are being in the preclinical and clinical trials.