Regulation of Carcinogenesis Angiogenesis and Metastasis by the Proprotein Convertases PC s

Regulation of Carcinogenesis  Angiogenesis and Metastasis by the Proprotein Convertases  PC s

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.

Author: Abdel-Majid Khatib

Publisher: Springer

ISBN: 1402047932

Category: Medical

Page: 157

View: 353

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.
Categories: Medical

Regulation of Carcinogenesis Angiogenesis and Metastasis by the Proprotein Convertases PC s

Regulation of Carcinogenesis  Angiogenesis and Metastasis by the Proprotein Convertases  PC s

Others MMPS are only suspected to be PCs substrates based on the presence ofa potentialPCs cleavage sites in their amino acid sequences (Tables 3–7). 1.3.1 Membrane-type matrix metalloproteases (MT-MMPs) Involved in metastasis, ...

Author: Abdel-Majid Khatib

Publisher: Springer Science & Business Media

ISBN: 9781402051326

Category: Medical

Page: 157

View: 595

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.
Categories: Medical

The Proprotein Convertases

The Proprotein Convertases

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

View: 453

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.
Categories: Science

The Role of Proprotein Convertases in Cancer

The Role of Proprotein Convertases in Cancer

"Cancer is a leading cause of death worldwide and accounts for about one fifth of all death in the Western world.

Author: Xiaowei Sun

Publisher:

ISBN: OCLC:922007993

Category:

Page:

View: 793

"Cancer is a leading cause of death worldwide and accounts for about one fifth of all death in the Western world. In 2008, nearly 12.7 million new cancer cases and 7.6 million cancer deaths occurred worldwide. The development of cancer is a multistage process, during which cells acquire a series of mutations that eventually lead to unrestrained cell growth, evasion of cell death, angiogenesis, invasion of the surrounding tissue and finally spreading to other parts of the body. The mammalian proprotein convertases (PCs) constitute a family of nine secretory serine proteases that are related to bacterial subtilisin and yeast kexin. They have been associated with cancer since the early 1990s. By processing cancer-associated factors, PCs are believed to play key roles in almost every step of cancer development. Seven of these PCs (PC1, PC2, furin, PC4, PC5/6, PACE4 and PC7) activate, or less frequently inactivate, a wide variety of substrates, including hormones, growth factors, receptors, adhesion molecules, angiogenic factors, metalloproteases. Among these substrates, some of them are key factors controlling cancer progression and metastasis. The last member of this family proprotein convertase subtilisin kexin 9 (PCSK9) only cleaves itself and participates in maintaining the levels of cholesterol, which was shown to have impacts on cancer incidence.In this thesis, I focused on the role of two PCs, PC5/6 and PCSK9, in cancer development. I first showed that PC5/6 is systematically down-regulated in human and mice intestinal tumors. In ApcMin/+ mice which are a colonic cancer model and develop numerous adenocarcinomas along the intestinal tract, the specific knockout of PC5/6 in the intestine and colon leads to higher number of tumors, particularly in duodenum. This suggests that PC5/6 plays a protective role against tumorigenesis in the intestine. Although PC5/6 is protective in intestinal cancer, it has been shown to promote tumor progression in other cancer types e.g., brain and skin. Interestingly, PC5/6 is inhibited by some natural inhibitors, the latent TGFbeta binding proteins 2 and 3 (LTBP-2, -3). These two proteins reduce the enzymatic activity of PC5/6A and reduce the bio-availability of PC5/6A by sequestering the zymogen proPC5/6 in the extracellular matrix. Finally, I demonstrated that the lack of PCSK9 leads to a significantly lower level of liver metastasis of melanoma cells. This cancer protective effect is due to low plasma cholesterol levels as well as high apoptosis in liver stroma and metastasized tumors that are associated with PCSK9 deficiency.In summary, the present cumulative data define some of the in vivo roles of PC5/6 and PCSK9 in cancer and should enhance our appreciation of the physiological impact of PC inhibition." --
Categories:

Non peptide Inhibitors of Proprotein Convertase Subtilisin Kexins PCSKs

Non peptide Inhibitors of Proprotein Convertase Subtilisin Kexins  PCSKs

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: 76

View: 229

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.
Categories: Science

Cumulated Index Medicus

Cumulated Index Medicus

Cancer Chemother Pharmacol 1995 ; Proprotein convertases ( PCI / PC ) and PC2 ) in normal and Helicobacter pylori in patients with gastric and nongastric ... Cancer Metastasis Rev 1994 Dec ; 13 ( 3-4 ) : 237-9 tumor - host interaction .

Author:

Publisher:

ISBN: UIUC:30112005408957

Category: Medicine

Page:

View: 750

Categories: Medicine

Index Medicus

Index Medicus

Author:

Publisher:

ISBN: OSU:32436011091459

Category: Medicine

Page: 2084

View: 111

Categories: Medicine

Cancer Research

Cancer Research

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 ...

Author:

Publisher:

ISBN: CORNELL:31924090587464

Category: Cancer

Page:

View: 767

Categories: Cancer

Proceedings of the American Association for Cancer Research

Proceedings of the American Association for Cancer Research

These results suggest that overexpression of furin leads to a more invasive phenotype . its metastasis - suppressed human chromosome ... Proprotein convertases are serine proteases that cleave proteins at the consensus sequence RRXRR .

Author: American Association for Cancer Research. Meeting

Publisher:

ISBN: NWU:35558004688962

Category: Cancer

Page:

View: 923

Contains abstracts of the scientific proceedings of the 73rd- annual meetings of the American Association for Cancer Research (1982- ).
Categories: Cancer