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Mechanisms involved in the induction of cell adhesion by hypoxia inducible factor

Research Project

Project/Area Number 17590258
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionAichi Cancer Center Research Institute

Principal Investigator

KANNAGI Reiji  Aichi Cancer Center, Department of Molecular Pathology, Program Head, 分子病態学部, 部長 (80161389)

Co-Investigator(Kenkyū-buntansha) TAGUCHI Osamu  Aichi Cancer Center, Department of Molecular Pathology, Section Chief, 分子病態学部, 室長 (00142167)
KYOGASHIMA Mamoru  Aichi Cancer Center, Department of Molecular Pathology, Research Scientist, 分子病態学部, 主任研究員 (50225091)
KANAMORI Akiko  Aichi Cancer Center, Department of Molecular Pathology, Research Scientist, 分子病態学部, 主任研究員 (00261173)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥2,400,000 (Direct Cost: ¥2,400,000)
KeywordsHIF / Transcriptional Regulation / sialic acid / sugar transporter / sialyltransferase / gene transfection / cell adhesion molecule / ganglioside
Research Abstract

Hypoxia figures heavily in pathophysiology of wide variety of diseases. In this research project we focused on induction mechanisms of genes encoding cell adhesion molecules by hypoxia. We found cell adhesion is markedly enhanced under hypoxic conditions. Transcriptional induction of genes for cell adhesion molecules by hypoxia is mediated mainly by a transcription factor, HIF (hypoxia inducible factor). As most cell adhesion molecules have carbohydrate side chains terminated by sialic acid residues, we focused on the effect of hypoxia on sialic acid metabolism. The cellular amount of sialic acid showed a significant increase under hypoxia, and this led to enhanced cell adhesion mediated by cell surface glycans carrying sialic acid residues. This was conferred by transcriptional induction of the gene for a sialic acid transporter, called Sialin. Transcription of genes for some sialyltransferases including ST3O was also enhanced by hypoxia, in addition to that of Sialin. HIF induced transcription of these genes, in some cases through collaboration with other transcription factors, and in some other cases solely by the action of HIF. It had been generally accepted that the cellular sialic acid pool is provided by de novo synthesis of sialic acid, but our present results indicated that incorporation of sialic acid through sialic acid transporter system also play an important role in supplying sialic acid residues required for synthesis of cell surface sialylated glycans. Hypoxia-induced Sialin transcription affected not only the synthesis of sialylated glycans on glycoproteins, but also that of gangliosides in various tissues and organs.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (24 results)

All 2007 2006 2005

All Journal Article (22 results) Book (2 results)

  • [Journal Article] Selectin-mediated metastasis of tumor cells : Alteration of carbohydrate-mediated cell-cell : interactions in cancers induced by epigenetic silencing of glycogenes.2007

    • Author(s)
      Kannagi, R., et al.
    • Journal Title

      Glycobiology (C.Sansom and O.Markman(eds.)) (Scion Publishing Ltd.)

      Pages: 274-287

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Quantitative RT-PCR analysis of sphingolipid metabolic enzymes in acute leukemia and myelodysplastic syndromes.2006

    • Author(s)
      Sobue, S., et al.
    • Journal Title

      Leukemia 20

      Pages: 2042-2046

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Identification of cutaneous lymphocyte-associated antigen as sialyl 6-sulfo Lewis x, a selectin ligand expressed on a subset of skin-homing helper memory T cells.2006

    • Author(s)
      Ohmori, K., et al.
    • Journal Title

      Blood 107

      Pages: 3197-3204

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] GATA-3/T-bet transcription factors regulates expression of sialyl Lewis X homing receptors on Th1/Th2 lymphocytes.2006

    • Author(s)
      Chen, G.-Y., Osada, H., Santamaria- Babi, L.F., Kannagi, R.
    • Journal Title

      Proc. Natl. Acad. Sci. U.S.A. 103

      Pages: 16894-16899

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Hypoxic culture induces expression of sialin, a sialic acid transporter, and cancer-associated gangliosides containing non-human sialic acid on human cancer cells.2006

    • Author(s)
      Yin, J., et al.
    • Journal Title

      Cancer Res. 66

      Pages: 2937-2945

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Interaction of GATA-3/T-bet transcription factors regulates expression of sialyl Lewis X homing receptors on Th1/Th2 lymphocytes.2006

    • Author(s)
      Chen, G.-Y., et al.
    • Journal Title

      Proc.Natl.Acad.Sci.USA. 103

      Pages: 16894-16899

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Hypoxic culture induces expression of sialin, a sialic acid transporter, and cancer-associated gangliosides containing non-human sialic acid on human cancer cells.2006

    • Author(s)
      Yin, J., Hashimoto, A., Izawa, M., Miyazaki, K., et al.
    • Journal Title

      Cancer Res. 66

      Pages: 2937-2945

    • Related Report
      2006 Annual Research Report
  • [Journal Article] quantitative RT-PCR analysis of sphingolipid metabolic enzymes in acute leukemia and myelodysplastic syndromes.2006

    • Author(s)
      Sobue, S., Iwasaki, T., Sugisaki, C., Nagata, K., et al.
    • Journal Title

      Leukemia 20

      Pages: 2042-2046

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Ectopic expression of N-acetylglucosamine 6-0-sulfotransferase 2 in chemotherapy-resistant ovarian adenocarcinomas.2006

    • Author(s)
      Kanoh, A., Seko, A., Ideo, H.et al.
    • Journal Title

      Glycoconj.J. 23

      Pages: 453-460

    • Related Report
      2006 Annual Research Report
  • [Journal Article] SHP-2-Erk signaling regulates Concanavalin A-dependent production of TIMP-2.2006

    • Author(s)
      Helal Uddin, BM, Hasegawa, H.H., Aminur, RM., et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 348

      Pages: 1145-1149

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Identification of cutaneous lymphocyte-associated antigen as sialyl 6-sulfo Lewis x, a selectin ligand expressed on a subset of skin-homing helper memory T cells.2006

    • Author(s)
      Ohmori, K., Fukui, F., Kiso, M., Imai, T., Yoshie, O., et al.
    • Journal Title

      Blood 107

      Pages: 3197-3204

    • Related Report
      2006 Annual Research Report
  • [Journal Article] GATA-3/T-bet transcription factors regulates expression of sialyl Lewis X homing receptors on Th1/Th2 lymphocytes.2006

    • Author(s)
      Chen, G.-Y., Osada, H., Santamaria- Babi, L.F., Kannagi, R.
    • Journal Title

      Proc.Natl.Acad.Sci.U.S.A. 103

      Pages: 16894-16899

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A major class of L-selectin ligands is eliminated in mice deficient in two sulfotransferases expressed in high endothelial venules2005

    • Author(s)
      Uchimura, K., et al.
    • Journal Title

      Nat. Immun. 6

      Pages: 1105-1113

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Synthesis of α(1,3)fucosyltransferases IV- and VII-dependent eosinophil selectin ligand and recruitment to the skin2005

    • Author(s)
      Satoh, T., Kanai, Y., et al.
    • Journal Title

      Am. J. Pathol. 167

      Pages: 787-796

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Hypoxic culture induces expression of sialin, a sialic acid transporter, and cancer-associated gangliosides containing non-human sialic acid on human cancer cells2005

    • Author(s)
      Yin, J., Hashimoto, A., et al.
    • Journal Title

      Cancer Res. 66

      Pages: 2937-2945

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] A major class of L-selectin ligands is eliminated in mice deficient in two sulfotransferases expressed in high endothelial venules.2005

    • Author(s)
      Uchimura, K., et al.
    • Journal Title

      Nat.Immunol 6

      Pages: 1105-1113

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Synthesis of a(1,3) fucosyl-transferases IV-and VII-dependent eosinophil selectin ligand and recruitment to the skin.2005

    • Author(s)
      Satoh, T., et al.
    • Journal Title

      Am.J.Pathol. 167

      Pages: 787-796

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Synthesis of α(1,3)fucosyltransferases IV- and VII-dependent eosinophil selectin ligand and recruitment to the skin2005

    • Author(s)
      Satoh, T., Kanai, Y., et al.
    • Journal Title

      Am.J Pathol. 167

      Pages: 787-796

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A major class of L-selectin ligands is eliminated in mice deficient in two sulfotransferases expressed in high endothelial venules2005

    • Author(s)
      Uchimura, K., et al.
    • Journal Title

      Nat.Immun. 6

      Pages: 1105-1113

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Expression of N-acetylglucosamine 6-O sulfotransferases (GlcNAc6STs)-1 and -4 in human monocytes : GlcNAc6ST-1 is implicated in the generation of the 6-sulfo N-acetyllactosamine/Lewis x epitope on CD44 and is induced by TNF-α2005

    • Author(s)
      Tjew, S.L., et al.
    • Journal Title

      Glycobiology 15

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Design and synthesis of a novel neo-glycolipid containing sialyl Lewis X determinant carried on the mucin GlcNAcbeta1-6GalNAcalpha core structure2005

    • Author(s)
      Otsubo, N., et al.
    • Journal Title

      Tetrahedron Asymmetry 16

      Pages: 1321-1327

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 6-O-Sulfo sialylparagloboside and sialyl Lewis X neo-glycolipids containing lactamized neuraminic acid : Synthesis and, antigenic reactivity against G159 monoclonal antibody2005

    • Author(s)
      Yamaguchi, M., et al.
    • Journal Title

      Glycoconj.J. 22

      Pages: 95-108

    • Related Report
      2005 Annual Research Report
  • [Book] Glycobiology2007

    • Author(s)
      Kannagi, R., et al.
    • Publisher
      Scion Publishing Ltd :, London, UK.
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] Glycobiology2006

    • Author(s)
      Kannagi, R., et al.
    • Publisher
      Scion Publishing Ltd:, London, UK.(in press)
    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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