Current model for the roles of TF, recombinant FVIIa, tumor-expressed FVII, and EPCR in cancer progression. Blood-borne FVII secreted by the liver binds to TF on the tumor cell surface (tumor cell indicated in pink) (left). The TF:FVIIa complex then activates PAR2 on the tumor cell surface, leading to the upregulation of proangiogenic factors such as CCL-2 and IL-8 and subsequent tumor growth. TF:FVIIa-mediated PAR2 activation also leads to the downregulation of EMT factors such as Slug and Sox9, resulting in an epithelial-like phenotype and diminished metastasis to the liver. Tumor cells produce FVII and FVIIa in an autocrine fashion, which binds to TF or EPCR (right). Tumor FVIIa in complex with TF activates PAR2 on the tumor cell surface (tumor cells indicated in blue), leading to the upregulation of proangiogenic factors such as CCL-2 and IL-8 and subsequent tumor growth. Tumor FVIIa bound to EPCR leads to the upregulation of EMT factors such as Slug and Sox9, resulting in mesenchymal-like phenotype and enhanced metastasis to the liver.