Regulation of Carcinogenesis, Angiogenesis and Metastasis by the Proprotein Convertases (PCs) A New Potential Strategy in Cancer Therapy Metastase-2 Vessel-2 Regulation of Carcinogenesis, Angiogenesis and Metastasis by the Proprotein ...

Author: Abdel-Majid Khatib

Publisher: Springer Science & Business Media

ISBN: 9781402051326

Category: Medical

Page: 157

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Convertases are widely expressed activating enzymes involved in various physiological and pathological processes. This book provides detailed and updated information on the role of these molecules in cancer. It is the first to summarize current knowledge of the importance of protein precursors maturation by the convertases in tumor progression, angiogenesis and metastasis. Each chapter discusses the importance of the convertases in the activation of various cancer-related molecules including growth factors, adhesion molecules and proteases.

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.

Author: Abdel-Majid Khatib

Publisher: Morgan & Claypool Publishers

ISBN: 9781615045365

Category: Science

Page: 86

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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.

3977–3981. doi:10.1016/j.bmcl.2010.04.101 [96] Khatib, Abdel-Majid (Ed.) (2006) Regulation ofcarcinogenesis, angiogenesis and metastasis by the proprotein convertases (PC's): A new potential strategy in cancer therapy, pp.

Author: Utpal Chandra De

Publisher: Biota Publishing

ISBN: 9781615044757

Category: Science

Page: 78

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The Ca+2-dependent mammalian Proprotein Convertase Subtilisin Kexins (PCSKs) or Proprotein/ Prohormone Convertases (PCs) are a family of endoproteases that play critical roles not only in normal development and metabolism but also in various physiological and pathological conditions. These were initiated by the proteolytic processing of large inactive proproteins into their shorter bioactive mature forms by the PCSK enzymes. These events take place in a highly selective, orchestrated, and stepwise manner. Among the various proprotein substrates of PCSK enzymes, particularly important are the precursor growth factors that include proPDGF-A, B, proIGF-1, 2 and proVEGF-C because of their strong implications in neoplasia initiation, progression, and metastasis. As a result of these findings, PCSK enzymes, particularly furin or PCSK3, became a major target for possible interventions of cancer via the use of their selective inhibitors. Significant progress has been accomplished in the development of peptide and protein-based PCSK inhibitors. However, non-peptide PCSK9 inhibitors are more preferable because of their drug-like and other characteristics. So far, a few non-peptide inhibitors of PCSK enzymes of various types of chemical structures have been described in the literature. These include (i) Carbocyclic compounds of diterpene and streptamine class. (ii) Nitrogen (N)-based heterocyclic compounds of various types and chemical structures such as (a) pyrrolidine bis piperazines, (b) Cu/Zn chelating terpyridine derivatives; (iii) Oxygen (O)-based Heterocyclic compounds of varying types of chemical structures such as (a) Flavonoids, (b) Coumarins of simple and dimeric types, (c) Quinonoids, (d) Iridoids; (iv) Aromatic compounds such as (a) Aryl guanidino and amidino derivatives, (b) Naphthyl fluorescein derivative, and (c) Phenyl Arsonic acids; and (v) C2-symmetrical aromatic azo-compounds. When measured against a small peptidyl-MCA fluorogenic substrate, these inhibitors displayed IC50 values ranging from nM to μM. A number of these inhibitors exhibited significant anti-PCSK activity when tested in ex vivo or cell culture conditions. This article provides an overall review of all non-peptide PCSK inhibitors so far reported in the literature along with those we identified recently for the first time and not yet published. The potential implications of these molecules as biochemical, therapeutical, or clinical agents will also be discussed.

J Cancer . 2003 Jun 2 ; 88 ( 11 ) : 1721-6 . for metastatic breast cancer . Miller KD . Clin Breast Cancer . ... J Diabetes The secretory proprotein convertases furin , PCs , and PC7 activate [ Inhibitation of tumor angiogenesis ...

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ISBN: OSU:32436011091459

Category: Medicine

Page: 2084

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Siegfried, G., Basak, A., Prichett-Pejic, W., Scamuffa, N., Ma, L., Benjannet, S., et al. (2005). Regulation of the stepwise proteolytic cleavage and secretion of PDGF-B by the proprotein convertases. Oncogene, 24, 6925–6935.

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Publisher: Academic Press

ISBN: 9780323854245

Category: Medical

Page: 266

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Stromal Signaling in Cancer, Volume 154 in the Advances in Cancer Research series, highlights new advances in the field, with this new volume presenting interesting chapters on a variety of timely topics surrounding cancer research. Each chapter is written by an international board of authors. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in the Advances in Cancer Research series Updated release includes the latest information on Stromal Signaling in Cancer

Conclusions ( 3rd of 3 parts ) ] Harguindey S. Carcinoma associated mucins : molecular biology and clinical ... Cancer Chemother Pharmacol 1995 ; Proprotein convertases ( PCI / PC ) and PC2 ) in normal and Helicobacter pylori in ...

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ISBN: UIUC:30112005408957

Category: Medicine

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J. Biol Chem . , 276 : by furin or its related PCs with a single specific cleavage at the COOH 4211-4217 ... W. G. Cancer metastasis and cleavage at N ° 7 - L does not result in the activation of proMMP - 2 , this angiogenesis : an ...

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ISBN: CORNELL:31924090587464

Category: Cancer

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