Tissue factor pathway inhibitor-2 (TFPI-2)—an underappreciated partaker in cancer and metastasis
Marek Z. Wojtukiewicz, M. Myśliwiec, Anna Tokajuk, Joanna Kruszewska, Barbara Polityńska, Anmbreen Jamroze, Anna M. Wojtukiewicz, Dean G. Tang, Kenneth V. Honn
Abstract
The coagulation system is known to play an important role in cancer development and metastasis, but the precise mechanisms by which it does so remain incompletely understood. With this in mind, we provide an updated overview of the effects of TFPI-2, a protease inhibitor, on cancer development and metastasis. TFPI-2 interacts with the thrombin cascade and also employs other mechanisms to suppress cancer growth and dissemination, which include extracellular matrix stabilization, promotion of caspase-mediated cell apoptosis, inhibition of angiogenesis and transduction of intracellular signals. Down-regulation of TFPI-2 expression is well documented in numerous types of neoplasms, mainly via promoter methylation. However, the exact role of TFPI-2 in cancer progression and possible approaches to up-regulate TFPI-2 expression warrant further studies. Strategies to reactivate TFPI-2 may represent a promising direction for future anticancer studies and therapy development.