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Identification of intracellular target molecules of glyco-genes and functional glycomics for those proteins

Research Project

Project/Area Number 13670121
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionOsaka University

Principal Investigator

MIYOSHI Eiji  Osaka University Graduate School of Medicine Div. Biochemistry, Associate Professor, 医学部, 助教授 (20322183)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsHepatocellular carcinoma / Haptoglobin / two-dimensional electrophoresis / GnT-III / GnT-V / Matriptase / Cancer Metastasis / Glycomics / がん転移 / ハプトグロビン / 血管新生 / βカテニン
Research Abstract

I identified intracellular target proteins for GnT-III and GnT-V and analyzed functions of those proteins. When DEN was administered to GnT-III transgenic mice, tumor formation in the liver was dramatically suppressed as compared to control mice. However, a few number of GnT-III transgenic mice treated with DEN had tumors. When serum proteins of those mice were analyzed by two-dimensional ectrophoresis followed by lectin blot, 6 target proteins for GnT-III were identified. One of these proteins was haptoglobin beta- chain. Haptoglobin is a radical scavenger and its function in terms of aberrant glycosylation should be clarified (Free Radical Research 36, 327-833, 2002). I also identified matriptase as a target molecule for GnT-V. Matriptase is one of membrane-anchored serine-protease, which has recently cloned. When GnT-V was transfected into a human gastric cancer cell MKN45, experimental metastasis was markedly promoted. The mechanism was due to induction of matriptase secretion because matriptase bearing beta1-6 GlcNAc branching, a product of GnT-V had a prolongation for degradation. This is the first answer for a question why GnT-V promotes cancer metastasis.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Kitada, T., Miyoshi, E., et al.: "Addition of bisecting N-acetylglucosamine residues to E-cadherin downregulates the tyrosine phosphorylation of β-catenin"J. Biol. Chem.. 276. 475-480 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Chakraborty A K, Miyoshi E, et al.: "Fusion-Hybrids with macrophage and melanoma cells up-regulate N-acetylglucosaminyltransferase V, β1-6 branching, and metastasis"Cell Growth and Differentiation. 12. 623-630 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ekuni A, Miyoshi E et al.: "A glycomic approach to hepatic tumors in N-acetylglucosaminyltransferase III (GnT-III) transgenic mice induced by diethylnitorsamine (DEN) : Identification of haptoglobin as a target molecule of GnT-III"Free Radical Research. 36. 827-833 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ihara S, Miyoshi E, et al.: "Prometastatic effect of N-acetylglucosaminyltransferase V is due to modification and stabilization of active matriptase by adding beta 1-6 GlcNAc branching"J. Biol. Chem.. 277. 16960-16967 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saito T, Miyoshi E, et al.: "A secreted type of beta 1,6-N-acetylglucosaminyltransferase V (GnT-V) induces tumor angiogenesis without mediation of glycosylation. A novel function of GnT-V distinct from the original glycosyltransferase"J. Biol. Chem.. 277. 17002-17008 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kitada, T. Miyoshi. E., Noda, K., Higashiyama, S., Ihara, H., Matsuura, N., Hayashi, N., Kawata, S., Matsuzawa, Y., and Taniguchi N.: "Addition of bisecting N-acetylglucosamine residues to: E-cadherin downregulates the tyrosine phosphotylation of β-catenin"J. Biol. Chem.. 276. 475-480 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Chakraborty A K, Pawelek J, Ikeda Y, Miyoshi E, Kolesnikova N, Funasaka Y, Ichihashi M, and Taniguchi N.: "Fusion-Hybrids with macrophage and melanoma cells up-regulate N-acetylglucosaminyltransferase V, β1-6 branching, and metastasis"Cell Growth and Differentiation. 12. 623-630 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ekuni A, Miyoshi E. Ko J H, Noda K, Kitada T, Ihara S, Endo T, Hino A, Honke K, and Taniguchi N: "A glycomic approach to hepatic tumors in N-acetylglucosaminyltransferase III (GnT-III) transgenic mice induced by diethylnitorsamine (DEN): Identification of haptoglobin as a target molecule of GnT-III"Free Radical Research. 36. 827-833 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ihara S, Miyoshi E, Ko JH, Murata K, Nakahara S, Honke K, Dickspn RB, Lin CY, Taniguchi N: "Prometastatic effect of N-acetylglucosaminyltransferase V is due to modification and stabilization of active matriptase by adding β 1-6 GlcNAc branching"J. Biol. Chem.. 277. 16960-16967 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saito T, Miyoshi E, Sasai K, Nakano N, Eguchi H, Honke K, Taniguchi N: "A secreted type of β 1,6-N-acetylglucosaminyltransferase V (GnT-V) induces tumor angiogenesis without mediation of glycosylation. A novel function of GnT-V distinct from the original glycosyltransferase"J. Biol. Chem.. 277. 17002-17008 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kitada, T., Miyoshi, E., et al.: "Addition of bisecting N-acetylglucosamine residues to E-cadherin downregulates the tyrosine phosphorylation of β-catenin"J.Biol.Chem.. 276. 475-480 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Chakraborty A K, Miyoshi E, et al.: "Fusion-Hybrids with macrophage and melanoma cells up-regulate N-acetylglucosaminyltransferase V, β1-6 branching, and metastasis"Cell Growth and Differentiation. 12. 623-630 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ekuni A, Miyoshi E et al.: "A glycomic approach to hepatic tumors in N-acetylglucosaminyltransferase III (GnT-III) transgenic mice induced by diethylnitorsamine (DEN) : Identification of haptoglobin as a target molecule of GnT-III"Free Radical Research. 36. 827-833 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ihara S, Miyoshi E, et al.: "Prometastatic effect of N-acetylglucosaminyltransferase V is due to modification and stabilization of active matriptase by adding beta 1-6 GlcNAc branching"J.Biol.Chem.. 277. 16960-16967 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Saito T, Miyoshi E, et al.: "A secreted type of beta 1,6-N-acetylglucosaminyltransferase V (GnT-V) induces tumor angiogenesis without mediation of glycosylation. A novel function of GnT-V distinct from -the original glvcosvltransferase"J.Biol.Chem.. 277. 17002-17008 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] T.Kitada, E.Miyoshi, N.Taniguchi et al.: "The addition of bisecting N-acetylglucosamine residues to E-cadherin downregulates the tyrosine phosphorylation of beta-catenin"J. Biol. Chem.. 276. 475-480 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] W.Wang, E.Miyamoto, N.Taniguchi et al.: "Ectopic expression of α 1, 6 fucosyltransferase in mice causes steatosis in the liver and kidney accompanied by a modification of lysosomal acid lipase"Glycobiology. 11. 165-174 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] N.Taniguchi, E.Miyoshi, et al.: "A glycomic approach to the identification and characterization of glycoprotein function in cells transfected with glycosyltransferase genes"Proteomics. 1. 239-247 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] A.K.Chakraborth, E.Miyoshi, H.Taniguchi et al.: "Fusion Hybrids with Macrophage and Melanoma Cells Up-Regulate N-Acetylglucosaminyltransferase V, β 1-6 Branching, and Metastasis"Cell Growth Differ. 12. 623-630 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Ito, E.Miyoshi, N.Taniguchi et al.: "Elevated expression of UDP-N-acetylglucosamine : alphamannoside beta 1, 6 N-acetylglucosaminyltransferase is an early event in hepatocarcinogenesis"Int. J. Cancer. 91. 631-637 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] T.Saito, E.Miyoshi, N.Taniguchi et al.: "A secreted type of β 1, 6-N-acetylglucosaminyltransferase V (GnT-V)induced tumor angiogenesis without mediation of glycosylation;---A novel function of GnT-V distinct from the original glycosyltransferase activity---"J. Biol. Chem.. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] A.Ekuni, E.Miyoshi, N.Taniguchi et al.: "A glycomic approach to hepatic tumors in N-acetylglucosaminyltransferase III (GnT-III) transgenic mice induced by diethylynitorsamine (DEN): Identification of haptoglogin as a target molecule of GnT-III"Free Rad. Res. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] S.Ihara, E.Miyoshi, N.Taniguchi et al.: "Pro-metastatic effect of N-acetylgucosaminyltransferase V is due to modification and stabilization of active matriptase by adding β1-6 GlcNAc-branching"J. Biol. Chem.. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] T.Saito, E.Miyoshi, N.Taniguchi et al.: "A secreted type of β 1, 6-N-acetylglucosaminyltransferase V (GnT-V)induced tumor angiogenesis without mediation of glycosylation;---A novel function of GnT-V distinct from the original glycosyltransferase activity---"J. Biol. Chem.. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] N.Taniguchi, E.Miyoshi, et al.: "Glycans in Cell Interaction and Recognition Therapeutic Aspects"The involvement of bisecting N-Acetylglucosamine in cancer. 73-88 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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