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Oncol Lett. 2011 Jul;2(4):599-608. Epub 2011 Apr 8.

Protease-activated receptors in cancer: A systematic review.

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Sir Run Run Shaw Institute of Clinical Medicine, Zhejiang University: Key Laboratory of Biotherapy of Zhejiang Province, Zhejiang University, Hangzhou, Zhejiang 310016.


The traditional view of the role of proteases in tumor growth, progression and metastasis has significantly changed. Apart from their contribution to cancer progression, it is evident that a subclass of proteases, such as thrombin, serves as signal molecules controlling cell functions through the protease-activated receptors (PARs). Among the four types of PAR (PAR1-4; cloned and named in order of their discovery), PAR1, PAR3 and PAR4 are activated by thrombin, unlike PAR2, which is activated by trypsin-like serine proteases. Thrombin has been proven to be a significant factor in both the behavior of cancer in its involvement in hemostasis and blood coagulation. Thrombin is a key supporter of various cellular effects relevant to tumor growth and metastasis, as well as a potent activator of angiogenesis, which is essential for the growth and development of all solid tumor types. This review presents an overview of the role of PAR-mediated thrombin in angiogenesis and cancer, focusing on the ability of PAR1- and PAR4-mediated thrombin to affect tumorigenesis and angiogenesis.

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