The Proprotein Convertases

The Proprotein Convertases
Discovery, Characteristics and Link to Tumor Progression, Angiogenesis and Metastasis

Abdel-Majid Khatib
ISBN: 9781615045365 | PDF ISBN: 9781615045372
Copyright © 2013 | 86 Pages | Publication Date: 02/01/2013

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Proprotein convertases (PCs) are a family of proteases including PC1, PC2, Furin, PC4, PACE4, PC5, and PC7. These enzymes are involved in the maturation of many precursor proteins involved in the process of tumorigenesis and metastasis. Since their discovery, PCs were suggested as potential targets for anti-cancer therapy, and their activity was found to directly affect tumor cell proliferation, migration invasion, and the malignant phenotypes of tumor cells. Here, we discuss a number of previous and recent findings on the PCs features, their implication in the regulation of multiple cellular functions that impact on the invasive/metastatic potential of cancer cells, and their clinical relevance in cancer patients.

Among the substrates of the proprotein convertases, various growth factors, their receptors, adhesion molecules, and proteases were identified. The PCs are inhibited by endogenous and exogenous inhibitors. To date, only pro7B2, a specific chaperone of PC2, and the granine-like precursor of neuroendocrine protein proSAAS, a selective ligand of PC1, have been identified as endogenous inhibitors of the PCs found in the regulated pathway. However, only PCs prosegments, several bioengineered inhibitors, peptides, and non-peptide compounds were found to inhibit the activity of the PCs found in the secretory pathway.

Table of Contents

Abbreviations
Discovery of Proprotein Convertases
Substrates of the Proprotein Convertases
Inhibitors of the Proprotein Convertases
Proprotein Convertases in Physiology and Pathology
Proprotein Convertases and Tumorigenesis
Acknowledgments
References
Author Biography
Titles of Related Interest

About the Author(s)

Abdel-Majid Khatib, University of Bordeaux, France
Dr. Khatib obtained his PhD from the University of Paris in 1997 and then completed his postdoctoral training at McGill University (Montreal, Canada). Starting in 2002, he directed his own laboratory as Scientist at the Ottawa Hospital Research Institute (OHRI), University of Ottawa (Ontario, Canada). Since 2008, he has been a research director at INSERM, first at the Hospital St-Louis in Paris and now at the University of Bordeaux. While a postdoctoral fellow, he demonstrated experimentally the implications of the proprotein convertases in the malignant phenotype of tumor cells. His work revealed at that time that the inhibition of the proprotein convertases may constitute a new potential opportunity in anticancer therapy. His research team has since discovered and characterized various substrates of these proteases and demonstrated the importance of their processing in the mediation of neoplasia. The laboratory of Dr. Khatib is also interested in the identification of small molecules inhibitors able to block the maturation of the PC substrates and reduce the malignant phenotype of tumor cells. Dr. Khatib has published many articles and reviews dealing with the importance of the proprotein convertases and their inhibitors in cancer.

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