Division of Hematology and Oncology, Department of Medicine, Thrombosis and Hemostasis Program, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Semin Thromb Hemost. 2019 Jun;45(4):385-395. doi: 10.1055/s-0039-1687894. Epub 2019 May 16.
There is a strong relationship between tissue factor (TF) and cancer. Many cancer cells express high levels of both full-length TF and alternatively spliced (as) TF. TF expression in cancer is associated with poor prognosis. In this review, the authors summarize the regulation of TF expression in cancer cells and the roles of TF and asTF in tumor growth and metastasis. A variety of different signaling pathways, transcription factors and micro ribonucleic acids regulate TF gene expression in cancer cells. The TF/factor VIIa complex enhances tumor growth by activating protease-activated receptor 2 signaling and by increasing the expression of angiogenic factors, such as vascular endothelial growth factor. AsTF increases tumor growth by enhancing integrin β1 signaling. TF and asTF also contribute to metastasis via multiple thrombin-dependent and independent mechanisms that include protecting tumor cells from natural killer cells. Finally, a novel anticancer therapy is using tumor TF as a target to deliver cytotoxic drugs to the tumor. TF may be useful in diagnosis, prognosis, and treatment of cancer.
组织因子（TF）与癌症之间存在很强的关系。许多癌细胞表达高水平的全长 TF 和选择性剪接（as）TF。癌症中 TF 的表达与预后不良有关。在这篇综述中，作者总结了癌细胞中 TF 表达的调节以及 TF 和 asTF 在肿瘤生长和转移中的作用。多种不同的信号通路、转录因子和 micro ribonucleic acids 调节癌细胞中 TF 基因的表达。TF/因子 VIIa 复合物通过激活蛋白酶激活受体 2 信号以及增加血管内皮生长因子等血管生成因子的表达来增强肿瘤生长。asTF 通过增强整合素 β1 信号来增加肿瘤生长。TF 和 asTF 还通过多种依赖和不依赖于凝血酶的机制促进转移，包括保护肿瘤细胞免受自然杀伤细胞的杀伤。最后，一种新的抗癌疗法是利用肿瘤 TF 作为靶点将细胞毒性药物递送到肿瘤中。TF 可能在癌症的诊断、预后和治疗中有用。
