The proteolytic profile of human cancer procoagulant suggests that it promotes cancer metastasis at the level of activation rather than degradation

The Protein Journal
Nalise Low Ah KeeCarminita L Frost

Abstract

Proteases are essential for tumour progression and many are over-expressed during this time. The main focus of research was the role of these proteases in degradation of the basement membrane and extracellular matrix (ECM), thereby enabling metastasis to occur. Cancer procoagulant (CP), a protease present in malignant tumours, but not normal tissue, is a known activator of coagulation factor X (FX). The present study investigated the function of CP in cancer progression by focussing on its enzymatic specificity. FX cleavage was confirmed using SDS-PAGE and MALDI-TOF MS and compared to the proteolytic action of CP on ECM proteins, including collagen type IV, laminin and fibronectin. Contrary to previous reports, CP cleaved FX at the conventional activation site (between Arg-52 and Ile-53). Additionally, degradation of FX by CP occurred at a much slower rate than degradation by conventional activators. Complete degradation of the heavy chain of FX was only visible after 24 h, while degradation by RVV was complete after 30 min, supporting postulations that the procoagulant function of CP may be of secondary importance to its role in cancer progression. Of the ECM proteins tested, only fibronectin was cleaved. The substrate specifi...Continue Reading

References

Sep 21, 1979·Biochimica Et Biophysica Acta·G RomeyM Lazdunski
Dec 1, 1991·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·S G Gordon, A M Mourad
Jan 1, 1994·Methods in Enzymology·S G Gordon
Jun 1, 1993·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·W P Mielicki, S G Gordon
Jul 15, 1997·Thrombosis Research·W P MielickiS G Gordon
May 18, 1999·Thrombosis Research·B OlasT Krajewski
Feb 19, 2000·Thrombosis Research·B OlasA Buczyński
Mar 21, 2000·Biochimica Et Biophysica Acta·P B Armstrong, M T Armstrong
Apr 3, 2001·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·S KabutoR J Naude
Jun 30, 2001·Cancer Letters·B OlasW P Mielicki
Sep 24, 2002·Journal of Cell Science·Roumen Pankov, Kenneth M Yamada
Jan 30, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yong-Jun YinRachel Bar-Shavit
Mar 15, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·Yong-Jun YinRachel Bar-Shavit
May 1, 2004·Arteriosclerosis, Thrombosis, and Vascular Biology·Nigel Mackman
May 18, 2005·British Journal of Plastic Surgery·David ChinWilliam B Coman
Mar 9, 2007·Journal of Cell Science·Puneeta AroraJoAnn Trejo
Mar 18, 2008·Biochemical and Biophysical Research Communications·Vishnu C Ramani, Randy S Haun
Oct 23, 2008·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Takashi Tsuruo, Naoya Fujita
Dec 3, 2008·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Antonella NaldiniFabio Carraro
Dec 6, 2008·International Journal of Cancer. Journal International Du Cancer·Valérie GratioDalila Darmoul
May 19, 2009·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Katarzyna Kaplinska, Wojciech P Mielicki

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Citations

Jul 19, 2017·Cancer Biology & Therapy·Ruishuang MaJialan Shi

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