LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 19

Search options

  1. Article ; Online: Identification of the myosin heavy polypeptide 9 as a downstream effector of the proprotein convertases in the human colon carcinoma HT-29 cells.

    Scamuffa, Nathalie / Metrakos, Peter / Calvo, Fabien / Khatib, Abdel-Majid

    Methods in molecular biology (Clifton, N.J.)

    2011  Volume 768, Page(s) 207–215

    Abstract: In addition to the large spectrum of the protein precursors processed and activated by the proprotein convertases (PCs) that are crucial for the maintenance of the malignant phenotype of colon cancer cells such as matrix metalloproteases, adhesion ... ...

    Abstract In addition to the large spectrum of the protein precursors processed and activated by the proprotein convertases (PCs) that are crucial for the maintenance of the malignant phenotype of colon cancer cells such as matrix metalloproteases, adhesion molecules, growth factors, and growth factor receptors, the PCs also regulate the expression and the activity of other proteins that are not PC substrates and involved in the acquisition of the metastatic and tumorigenic potential of these tumor cells. The identification in colon cancer cells of such proteins is thereby crucial for the understanding of the cascade of molecular events regulated by the PCs leading to tumorigenesis and metastasis and thus may constitute potential candidates for new colon cancer-specific targets and/or biomarkers. Using the human colon cancer cells HT-29 and ProteinChip arrays analysis that apply the surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS), we identified the myosin heavy polypeptide 9 as new downstream effector of PCs in these cells. This protein was reported to be involved in the processes of malignant epithelial transformation and its role in colon cancer is unknown.
    MeSH term(s) Colonic Neoplasms/enzymology ; Colonic Neoplasms/pathology ; HT29 Cells ; Humans ; Myosin Heavy Chains/analysis ; Myosin Heavy Chains/metabolism ; Proprotein Convertases/antagonists & inhibitors ; Proprotein Convertases/metabolism ; Protein Array Analysis/methods ; Protein Precursors/metabolism ; Serine Proteinase Inhibitors/pharmacology ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods ; Substrate Specificity/physiology ; Trypsin Inhibitors/pharmacology ; alpha 1-Antitrypsin/pharmacology
    Chemical Substances Protein Precursors ; Serine Proteinase Inhibitors ; Trypsin Inhibitors ; alpha 1-Antitrypsin ; alpha 1-antitrypsin Portland ; Proprotein Convertases (EC 3.4.21.-) ; Myosin Heavy Chains (EC 3.6.4.1)
    Language English
    Publishing date 2011
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-61779-204-5_10
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  2. Article ; Online: Prodomain of the proprotein convertase subtilisin/kexin Furin (ppFurin) protects from tumor progression and metastasis.

    Scamuffa, Nathalie / Sfaxi, Fatma / Ma, Jia / Lalou, Claude / Seidah, Nabil / Calvo, Fabien / Khatib, Abdel-Majid

    Carcinogenesis

    2014  Volume 35, Issue 3, Page(s) 528–536

    Abstract: Proteolytic maturation of various precursor proteins by the proprotein convertase Furin is now considered as a crucial step in tumor progression and metastasis. Here, we report the repression of the malignant and metastatic potential of carcinoma cells ... ...

    Abstract Proteolytic maturation of various precursor proteins by the proprotein convertase Furin is now considered as a crucial step in tumor progression and metastasis. Here, we report the repression of the malignant and metastatic potential of carcinoma cells by the prodomain region of Furin (ppFurin), a naturally occurring inhibitor of this convertase. Overexpression of ppFurin in carcinoma cells in a stable manner significantly reduced their convertase activity and ability to mediate processing of the Furin cancer-related substrates platelet-derived growth factor (PDGF)-A and insulin-like growth factor-I receptor precursors. Unprocessed platelet-derived growth factor-A produced by ppFurin expressing cells failed to induce the activation of Akt in the platelet-derived growth factor receptor-expressing cells NIH BALB/c-3T3 and treatment of ppFurin expressing cells with insulin-like growth factor-I failed to induce Akt phosphorylation, compared with controls. The malignant potential of ppFurin expressing cells was significantly reduced as revealed by the loss of anchorage-independent growth and survival that associated their increased chemosensitivity. In vivo, comparative studies revealed that expression of ppFurin in the carcinoma cells MDA-MB-231 and CT-26 cells inhibited tumor growth when subcutaneously inoculated in nude mice. The use of an experimental liver colorectal metastasis model revealed the reduced ability of metastatic carcinoma CT-26 cells to colonize the liver in response to intrasplenic/portal inoculation. Further analyses revealed reduced Furin activity in tumors derived from intrasplenic inoculated mice with ppFurin expressing CT-26 cells. This finding highlights the role of Furin in the malignant and metastatic potential of tumor cells and suggests the possible consideration of using its naturally occurring inhibitor ppFurin in anticancer therapy.
    MeSH term(s) Animals ; Cell Line, Tumor ; Disease Progression ; Humans ; Mice ; Mice, Inbred BALB C ; NIH 3T3 Cells ; Neoplasm Metastasis ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism ; Subtilisins/chemistry ; Subtilisins/physiology
    Chemical Substances Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Subtilisins (EC 3.4.21.-)
    Language English
    Publishing date 2014-03
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 603134-1
    ISSN 1460-2180 ; 0143-3334
    ISSN (online) 1460-2180
    ISSN 0143-3334
    DOI 10.1093/carcin/bgt345
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  3. Article: Potential opportunity in the development of new therapeutic agents based on endogenous and exogenous inhibitors of the proprotein convertases.

    Bontemps, Yannick / Scamuffa, Nathalie / Calvo, Fabien / Khatib, Abdel-Majid

    Medicinal research reviews

    2006  Volume 27, Issue 5, Page(s) 631–648

    Abstract: The proprotein convertases (PCs) are responsible for the endoproteolytic processing of various protein precursors (e.g., growth factors, receptors, adhesion molecules, and matrix metalloproteinases) implicated in several diseases such as obesity, ... ...

    Abstract The proprotein convertases (PCs) are responsible for the endoproteolytic processing of various protein precursors (e.g., growth factors, receptors, adhesion molecules, and matrix metalloproteinases) implicated in several diseases such as obesity, diabetes, atherosclerosis, cancer, and Alzheimer disease. The potential clinical and pharmacological role of the PCs has fostered the development of various PC-inhibitors. In this review we summarized the recent findings on PCs inhibitors, their mode of actions and potential use in the therapy of various diseases.
    MeSH term(s) Humans ; Models, Biological ; Models, Molecular ; Proprotein Convertases/antagonists & inhibitors ; Proprotein Convertases/metabolism ; Protease Inhibitors/chemistry ; Protease Inhibitors/therapeutic use
    Chemical Substances Protease Inhibitors ; Proprotein Convertases (EC 3.4.21.-)
    Keywords covid19
    Language English
    Publishing date 2006-07-25
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 603210-2
    ISSN 0198-6325
    ISSN 0198-6325
    DOI 10.1002/med.20072
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  4. Article ; Online: Repression of liver colorectal metastasis by the serpin Spn4A a naturally occurring inhibitor of the constitutive secretory proprotein convertases.

    Sfaxi, Fatma / Scamuffa, Nathalie / Lalou, Claude / Ma, Jia / Metrakos, Peter / Siegfried, Géraldine / Ragg, Hermann / Bikfalvi, Andreas / Calvo, Fabien / Khatib, Abdel-Majid

    Oncotarget

    2014  Volume 5, Issue 12, Page(s) 4195–4210

    Abstract: Liver is the most common site of metastasis from colorectal cancers, and liver of patients with liver colorectal metastasis have abnormal levels of the proprotein convertases (PCs). These proteases are involved in the activation and/or expression of ... ...

    Abstract Liver is the most common site of metastasis from colorectal cancers, and liver of patients with liver colorectal metastasis have abnormal levels of the proprotein convertases (PCs). These proteases are involved in the activation and/or expression of various colon cancer-related mediators, making them promising targets in colorectal liver metastasis therapy. Here, we revealed that the serpin Spn4 from Drosophila melanogaster inhibits the activity of all the PCs found in the constitutive secretory pathway and represses the metastatic potential of the colon cancer cells HT-29 and CT-26. In these cells, Spn4A inhibited the processing of the PCs substrates IGF-1R and PDGF-A that associated their reduced anchorage-independent growth, invasiveness and survival in response to apoptotic agents. In vivo, Spn4A-expressing tumor cells showed repressed subcutaneous tumor development and liver metastases formation in response to their intrasplenic inoculation. In these cells Spn4A induced the expression of molecules with anti-metastatic functions and inhibited expression of pro-tumorigenic molecules. Taken together, our findings identify Spn4A as the only endogenous inhibitor of all the constitutive secretory pathway PCs, which is able to repress the metastatic potential of colon cancer cells. These results suggest the potential use of Spn4A and/or derivates as a useful adduct colorectal liver metastasis prevention.
    MeSH term(s) Adenocarcinoma/genetics ; Adenocarcinoma/pathology ; Apoptosis Regulatory Proteins ; Cell Proliferation ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/pathology ; Humans ; Mitochondrial Proteins ; Neoplasm Metastasis ; Proprotein Convertases/genetics ; Proprotein Convertases/metabolism ; Serpins/metabolism ; Transfection
    Chemical Substances Apopt1 protein, mouse ; Apoptosis Regulatory Proteins ; Mitochondrial Proteins ; Serpins ; Proprotein Convertases (EC 3.4.21.-)
    Language English
    Publishing date 2014-06-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2560162-3
    ISSN 1949-2553 ; 1949-2553
    ISSN (online) 1949-2553
    ISSN 1949-2553
    DOI 10.18632/oncotarget.1966
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  5. Article: Proprotein convertases: lessons from knockouts

    Scamuffa, Nathalie / Calvo, Fabien / Chrétien, Michel / Seidah, Nabil G / Khatib, Abdel-Majid

    FASEB journal. 2006 Oct., v. 20, no. 12

    2006  

    Abstract: ... neurodegenerative diseases.--Scamuffa, N., Calvo, F., Chrétien, M., Seidah, N. G., Khatib, A-M. Proprotein convertases ...

    Abstract The physiological role of the subtilisin/kexin-like proprotein convertases (PCs) in rodents has been examined through the use of knockout mice. This review will summarize the major in vivo defects that result from the disruption of the expression of their genes. This includes abnormal embryonic development, hormonal disorder, infertility, and/or modified lipid/sterol metabolism. Members of the PC family play a central role in the processing of various protein precursors ranging from hormones and growth factors to bacterial toxins and viral glycoproteins. Proteolysis occurring at basic residues is mediated by the basic amino acid-specific proprotein convertases, namely: PC1/3, PC2, furin, PACE4, PC4, PC5/6, and PC7. In contrast, proteolysis at nonbasic residues is performed by the subtilisin/kexin-like isozyme-1 (SKI-1/S1P) and the newly identified neural apoptosis-regulated convertase-1 (PCSK9/NARC-1). In addition to their requirement for many physiological processes, these enzymes are also involved in various pathologies such as cancer, obesity, diabetes, lipid disorders, infectious diseases, atherosclerosis and neurodegenerative diseases.--Scamuffa, N., Calvo, F., Chrétien, M., Seidah, N. G., Khatib, A-M. Proprotein convertases: lessons from knockouts.
    Language English
    Dates of publication 2006-10
    Size p. 1954-1963.
    Publishing place The Federation of American Societies for Experimental Biology
    Document type Article
    ZDB-ID 639186-2
    ISSN 1530-6860 ; 0892-6638
    ISSN (online) 1530-6860
    ISSN 0892-6638
    Database NAL-Catalogue (AGRICOLA)

    More links

    Kategorien

  6. Article ; Online: Proprotein convertases: lessons from knockouts.

    Scamuffa, Nathalie / Calvo, Fabien / Chrétien, Michel / Seidah, Nabil G / Khatib, Abdel-Majid

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology

    2006  Volume 20, Issue 12, Page(s) 1954–1963

    Abstract: The physiological role of the subtilisin/kexin-like proprotein convertases (PCs) in rodents has been examined through the use of knockout mice. This review will summarize the major in vivo defects that result from the disruption of the expression of ... ...

    Abstract The physiological role of the subtilisin/kexin-like proprotein convertases (PCs) in rodents has been examined through the use of knockout mice. This review will summarize the major in vivo defects that result from the disruption of the expression of their genes. This includes abnormal embryonic development, hormonal disorder, infertility, and/or modified lipid/sterol metabolism. Members of the PC family play a central role in the processing of various protein precursors ranging from hormones and growth factors to bacterial toxins and viral glycoproteins. Proteolysis occurring at basic residues is mediated by the basic amino acid-specific proprotein convertases, namely: PC1/3, PC2, furin, PACE4, PC4, PC5/6, and PC7. In contrast, proteolysis at nonbasic residues is performed by the subtilisin/kexin-like isozyme-1 (SKI-1/S1P) and the newly identified neural apoptosis-regulated convertase-1 (PCSK9/NARC-1). In addition to their requirement for many physiological processes, these enzymes are also involved in various pathologies such as cancer, obesity, diabetes, lipid disorders, infectious diseases, atherosclerosis and neurodegenerative diseases.
    MeSH term(s) Animals ; Cardiovascular System/embryology ; Cardiovascular System/growth & development ; Embryo, Mammalian ; Heart Diseases/enzymology ; Heart Diseases/etiology ; Mice ; Mice, Knockout ; Proprotein Convertases/antagonists & inhibitors ; Proprotein Convertases/deficiency ; Proprotein Convertases/metabolism ; Proprotein Convertases/physiology ; Substrate Specificity
    Chemical Substances Proprotein Convertases (EC 3.4.21.-)
    Keywords covid19
    Language English
    Publishing date 2006-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 639186-2
    ISSN 1530-6860 ; 0892-6638
    ISSN (online) 1530-6860
    ISSN 0892-6638
    DOI 10.1096/fj.05-5491rev
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  7. Article: Opposing function of the proprotein convertases furin and PACE4 on breast cancer cells' malignant phenotypes: role of tissue inhibitors of metalloproteinase-1.

    Lapierre, Marion / Siegfried, Geraldine / Scamuffa, Nathalie / Bontemps, Yannick / Calvo, Fabien / Seidah, Nabil G / Khatib, Abdel-Majid

    Cancer research

    2007  Volume 67, Issue 19, Page(s) 9030–9034

    Abstract: Proteolytic cleavage of various cancer-related substrates by the proprotein convertases (PC) was reported to be important in the processes of neoplasia. These enzymes are inhibited by their naturally occurring inhibitors, the prosegments (ppPC), and by ... ...

    Abstract Proteolytic cleavage of various cancer-related substrates by the proprotein convertases (PC) was reported to be important in the processes of neoplasia. These enzymes are inhibited by their naturally occurring inhibitors, the prosegments (ppPC), and by the engineered general PC inhibitor, the serpin variant alpha1-PDX. In the present study, we sought to compare the effect of these PC inhibitors on malignant phenotypes of breast cancer cells. Overexpression in a stable manner of alpha1-PDX and the prosegment ppPACE4 in MDA-MB-231 breast cancer cells resulted in increased matrix metalloproteinase (MMP)-9 (but not MMP-2) activity and a reduced secretion of tissue inhibitor of metalloproteinase 1 (TIMP-1). This was associated with significant enhancement in cell motility, migration, and invasion of collagen in vitro. In contrast, ppFurin expression in these cells decreased MMP-9 activity and diminished these biological functions, but had no significant effect on TIMP-1 secretion. Taken together, these data showed the specific and opposing roles of Furin and PACE4 in the regulation of MMP-9/TIMP-1-mediated cell motility and invasion.
    MeSH term(s) Breast Neoplasms/enzymology ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Cell Movement/physiology ; Collagen/metabolism ; Furin/biosynthesis ; Furin/genetics ; Furin/metabolism ; Humans ; Matrix Metalloproteinase 2/metabolism ; Matrix Metalloproteinase 9/metabolism ; Neoplasm Invasiveness ; Proprotein Convertases/biosynthesis ; Proprotein Convertases/genetics ; Proprotein Convertases/metabolism ; Protein Precursors/biosynthesis ; Protein Precursors/genetics ; Protein Precursors/metabolism ; Serine Endopeptidases/biosynthesis ; Serine Endopeptidases/genetics ; Serine Endopeptidases/metabolism ; Tissue Inhibitor of Metalloproteinase-1/metabolism ; Tissue Inhibitor of Metalloproteinase-1/secretion ; Transfection ; alpha 1-Antitrypsin/genetics
    Chemical Substances Protein Precursors ; Tissue Inhibitor of Metalloproteinase-1 ; alpha 1-Antitrypsin ; Collagen (9007-34-5) ; PCSK6 protein, human (EC 3.4.21.-) ; Proprotein Convertases (EC 3.4.21.-) ; Serine Endopeptidases (EC 3.4.21.-) ; FURIN protein, human (EC 3.4.21.75) ; Furin (EC 3.4.21.75) ; Matrix Metalloproteinase 2 (EC 3.4.24.24) ; Matrix Metalloproteinase 9 (EC 3.4.24.35)
    Language English
    Publishing date 2007-10-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1432-1
    ISSN 1538-7445 ; 0008-5472
    ISSN (online) 1538-7445
    ISSN 0008-5472
    DOI 10.1158/0008-5472.CAN-07-0807
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  8. Article: Selective inhibition of proprotein convertases represses the metastatic potential of human colorectal tumor cells.

    Scamuffa, Nathalie / Siegfried, Geraldine / Bontemps, Yannick / Ma, Liming / Basak, Ajoy / Cherel, Ghislaine / Calvo, Fabien / Seidah, Nabil G / Khatib, Abdel-Majid

    The Journal of clinical investigation

    2007  Volume 118, Issue 1, Page(s) 352–363

    Abstract: The proprotein convertases (PCs) are implicated in the activation of various precursor proteins that play an important role in tumor cell metastasis. Here, we report their involvement in the regulation of the metastatic potential of colorectal tumor ... ...

    Abstract The proprotein convertases (PCs) are implicated in the activation of various precursor proteins that play an important role in tumor cell metastasis. Here, we report their involvement in the regulation of the metastatic potential of colorectal tumor cells. PC function in the human and murine colon carcinoma cell lines HT-29 and CT-26, respectively, was inhibited using siRNA targeting the PCs furin, PACE4, PC5, and PC7 or by overexpression of the general PC inhibitor alpha1-antitrypsin Portland (alpha1-PDX). We found that overexpression of alpha1-PDX and knockdown of furin expression inhibited processing of IGF-1 receptor and its subsequent activation by IGF-1 to induce IRS-1 and Akt phosphorylation, all important in colon carcinoma metastasis. These data suggest that the PC furin is a major IGF-1 receptor convertase. Expression of alpha1-PDX reduced the production of TNF-alpha and IL-1alpha by human colon carcinoma cells, and incubation of murine liver endothelial cells with conditioned media derived from these cells failed to induce tumor cell adhesion to activated murine endothelial cells, a critical step in metastatic invasion. Furthermore, colon carcinoma cells in which PC activity was inhibited by overexpression of alpha1-PDX when injected into the portal vein of mice showed a significantly reduced ability to form liver metastases. This suggests that inhibition of PCs is a potentially promising strategy for the prevention of colorectal liver metastasis.
    MeSH term(s) Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Cell Adhesion/genetics ; Cell Line, Tumor ; Colorectal Neoplasms/enzymology ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/prevention & control ; Humans ; Insulin Receptor Substrate Proteins ; Interleukin-1beta/biosynthesis ; Interleukin-1beta/genetics ; Liver Neoplasms/enzymology ; Liver Neoplasms/genetics ; Liver Neoplasms/pathology ; Liver Neoplasms/prevention & control ; Liver Neoplasms/secondary ; Mice ; Neoplasm Metastasis ; Proprotein Convertases/antagonists & inhibitors ; Proprotein Convertases/genetics ; Proprotein Convertases/metabolism ; Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; Receptor, IGF Type 1/genetics ; Receptor, IGF Type 1/metabolism ; Tumor Necrosis Factor-alpha/biosynthesis ; Tumor Necrosis Factor-alpha/genetics ; alpha 1-Antitrypsin/biosynthesis ; alpha 1-Antitrypsin/genetics ; alpha 1-Antitrypsin/pharmacology
    Chemical Substances Adaptor Proteins, Signal Transducing ; IRS1 protein, human ; Insulin Receptor Substrate Proteins ; Interleukin-1beta ; Irs1 protein, mouse ; Tumor Necrosis Factor-alpha ; alpha 1-Antitrypsin ; Receptor, IGF Type 1 (EC 2.7.10.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Proprotein Convertases (EC 3.4.21.-)
    Language English
    Publishing date 2007-12-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI32040
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  9. Article ; Online: Inhibition of the proprotein convertases represses the invasiveness of human primary melanoma cells with altered p53, CDKN2A and N-Ras genes.

    Lalou, Claude / Scamuffa, Nathalie / Mourah, Samia / Plassa, Francois / Podgorniak, Marie-Pierre / Soufir, Nadem / Dumaz, Nicolas / Calvo, Fabien / Basset-Seguin, Nicole / Khatib, Abdel-Majid

    PloS one

    2010  Volume 5, Issue 4, Page(s) e9992

    Abstract: Background: Altered tumor suppressor p53 and/or CDKN2A as well as Ras genes are frequently found in primary and metastatic melanomas. These alterations were found to be responsible for acquisition of invasive and metastatic potential through their ... ...

    Abstract Background: Altered tumor suppressor p53 and/or CDKN2A as well as Ras genes are frequently found in primary and metastatic melanomas. These alterations were found to be responsible for acquisition of invasive and metastatic potential through their defective regulatory control of metalloproteinases and urokinase genes.
    Methodology/principal findings: Using primary human melanoma M10 cells with altered p53, CDKN2A and N-Ras genes, we found that inhibition of the proprotein convertases (PCs), enzymes involved in the proteolytic activation of various cancer-related protein precursors resulted in significantly reduced invasiveness. Analysis of M10 cells and their gastric and lymph node derived metastatic cells revealed the presence of all the PCs found in the secretory pathway. Expression of the general PCs inhibitor alpha1-PDX in these cells in a stable manner (M10/PDX) had no effect on the mRNA expression levels of these PCs. Whereas, in vitro digestion assays and cell transfection experiments, revealed that M10/PDX cells display reduced PCs activity and are unable to process the PCs substrates proIGF-1R and proPDGF-A. These cells showed reduced migration and invasion that paralleled decreased gelatinase MMP-2 activity and increased expression and secretion of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2. Furthermore, these cells showed decreased levels of urokinase-type plasminogen activator receptor (uPAR) and increased levels of plasminogen activator inhibitor-1 (PAI-1).
    Conclusions: Taken together, these data suggest that inhibition of PCs activity results in decreased invasiveness of primary human melanoma cells despite their altered p53, CDKN2A and N-Ras genes, suggesting that PCs may serve as novel therapeutic targets in melanoma.
    MeSH term(s) Genes, p16 ; Genes, p53/genetics ; Genes, ras/genetics ; Humans ; Lymph Nodes/pathology ; Matrix Metalloproteinase 2/metabolism ; Matrix Metalloproteinase Inhibitors ; Melanoma/enzymology ; Melanoma/genetics ; Melanoma/pathology ; Neoplasm Invasiveness ; Proprotein Convertases/antagonists & inhibitors ; Stomach/pathology ; Tumor Cells, Cultured ; alpha 1-Antitrypsin/pharmacology
    Chemical Substances Matrix Metalloproteinase Inhibitors ; alpha 1-Antitrypsin ; alpha 1-antitrypsin Portland ; Proprotein Convertases (EC 3.4.21.-) ; Matrix Metalloproteinase 2 (EC 3.4.24.24)
    Language English
    Publishing date 2010-04-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0009992
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  10. Article ; Online: Zebrafish ProVEGF-C expression, proteolytic processing and inhibitory effect of unprocessed ProVEGF-C during fin regeneration.

    Khatib, Abdel-Majid / Lahlil, Rachid / Scamuffa, Nathalie / Akimenko, Marie-Andrée / Ernest, Sylvain / Lomri, Abdderahim / Lalou, Claude / Seidah, Nabil G / Villoutreix, Bruno O / Calvo, Fabien / Siegfried, Geraldine

    PloS one

    2010  Volume 5, Issue 7, Page(s) e11438

    Abstract: Background: In zebrafish, vascular endothelial growth factor-C precursor (proVEGF-C) processing occurs within the dibasic motif HSIIRR(214) suggesting the involvement of one or more basic amino acid-specific proprotein convertases (PCs) in this process. ...

    Abstract Background: In zebrafish, vascular endothelial growth factor-C precursor (proVEGF-C) processing occurs within the dibasic motif HSIIRR(214) suggesting the involvement of one or more basic amino acid-specific proprotein convertases (PCs) in this process. In the present study, we examined zebrafish proVEGF-C expression and processing and the effect of unprocessed proVEGF-C on caudal fin regeneration.
    Methodology/principal findings: Cell transfection assays revealed that the cleavage of proVEGF-C, mainly mediated by the proprotein convertases Furin and PC5 and to a less degree by PACE4 and PC7, is abolished by PCs inhibitors or by mutation of its cleavage site (HSIIRR(214) into HSIISS(214)). In vitro, unprocessed proVEGF-C failed to activate its signaling proteins Akt and ERK and to induce cell proliferation. In vivo, following caudal fin amputation, the induction of VEGF-C, Furin and PC5 expression occurs as early as 2 days post-amputation (dpa) with a maximum levels at 4-7 dpa. Using immunofluorescence staining we localized high expression of VEGF-C and the convertases Furin and PC5 surrounding the apical growth zone of the regenerating fin. While expression of wild-type proVEGF-C in this area had no effect, unprocessed proVEGF-C inhibited fin regeneration.
    Conclusions/significances: Taken together, these data indicate that zebrafish fin regeneration is associated with up-regulation of VEGF-C and the convertases Furin and PC5 and highlight the inhibitory effect of unprocessed proVEGF-C on fin regeneration.
    MeSH term(s) Animals ; Animals, Genetically Modified/genetics ; Animals, Genetically Modified/metabolism ; Animals, Genetically Modified/physiology ; Blotting, Western ; Cell Proliferation ; Cells, Cultured ; Furin/genetics ; Furin/metabolism ; Phosphorylation ; Polymerase Chain Reaction ; Proprotein Convertase 5/genetics ; Proprotein Convertase 5/metabolism ; Regeneration/genetics ; Regeneration/physiology ; Tyrosine/metabolism ; Vascular Endothelial Growth Factor C/genetics ; Vascular Endothelial Growth Factor C/metabolism ; Zebrafish/genetics ; Zebrafish/metabolism ; Zebrafish/physiology ; Zebrafish Proteins/genetics ; Zebrafish Proteins/metabolism
    Chemical Substances Vascular Endothelial Growth Factor C ; Zebrafish Proteins ; Tyrosine (42HK56048U) ; Proprotein Convertase 5 (EC 3.4.21.-) ; Furin (EC 3.4.21.75)
    Language English
    Publishing date 2010-07-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0011438
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

To top