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2013 Fiscal Year Final Research Report

Intracellular transport and function of cancer- and neurodegenerative disease-related glycosphingolipids

Research Project

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Project/Area Number 22790280
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field General medical chemistry
Research InstitutionNagoya University

Principal Investigator

YAMAUCHI Yoshio  名古屋大学, 医学(系)研究科(研究院), 講師 (00444878)

Project Period (FY) 2010-10-20 – 2014-03-31
Keywordsスフィンゴ糖脂質 / ガングリオシド / がん / 神経変成疾患
Research Abstract

Glycosphingolipids (GSLs) are involved in pathophysiology of cancer and neurodegenerative disorders. In this work, I studied cellular distribution and functionalities of gangliosides associated to malanoma, a skin cancer and to Niemann-Pick type C (NPC) disease, a neurodegenerative disorder. The results showed that the melanoma-associated antigen ganglioside GD3 plays a role in the activation of the regulatory factor involved in lipid biosynthesis, which promotes lipid biosynthesis for the integrity of membrane microdomains in human melanoma cells. Pharmacological inhibition of the regulatory factor prevented tumor growth. Also, I studied cellular distribution of gangliosides related to NPC disease in NPC cells. The results showed that disease-associated gangliosides accumulate in the lysosome. Several small-molecules that promote their redistribution from the lysosome to cell surface were identified.

  • Research Products

    (18 results)

All 2012 2011 2010

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (10 results)

  • [Journal Article] Fine tuning of cell signals by glycosylation2012

    • Author(s)
      Furukawa K, Ohkawa Y, Yamauchi Y, Hamamura K, Ohmi Y, Furukawa K.
    • Journal Title

      J Biochem.

      Volume: 151 Pages: 573-578

    • DOI

      10.1093/jb/mvs043

    • Peer Reviewed
  • [Journal Article] Essential roles of gangliosides in the formation and maintenance of membrane microdomains in brain tissues2012

    • Author(s)
      Ohmi Y, Ohkawa Y, Yamauchi Y, Tajima O, Furukawa K, Furukawa K.
    • Journal Title

      Neurochem Res.

      Volume: 37 Pages: 1185-1191

    • DOI

      10.1007/s11064-012-0764-7

    • Peer Reviewed
  • [Journal Article] Wisp2/CCN5 up-regulated in the central nervous system of GM3-only mice facilitates neurite formation in Neuro2a cells via integrin-Akt signaling2011

    • Author(s)
      Ohkawa Y, Ohmi Y, Tajima O, Yamauchi Y, Furukawa K, Furukawa K.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 411 Pages: 483-489

    • DOI

      10.1016/j.bbrc.2011.06.118

    • Peer Reviewed
  • [Journal Article] Functional activation of Src family kinase yes protein is essential for the enhanced malignant properties of human melanoma cells expressing ganglioside GD32011

    • Author(s)
      Hamamura K, Tsuji M, Hotta H, Ohkawa Y, Takahashi M, Shibuya H, Nakashima H, Yamauchi Y, Hashimoto N, Hattori H, Ueda M, Furukawa K, Furukawa K.
    • Journal Title

      J Biol Chem.

      Volume: 286 Pages: 18526-18537

    • DOI

      10.1074/jbc.M110.164798

    • Peer Reviewed
  • [Journal Article] Positive feedback loop between PI3K-Akt-mTORC1 signaling and the lipogenic pathway boosts Akt signaling : induction of the lipgenic pathway by a melanoma antigen2011

    • Author(s)
      Yamauchi Y, Furukawa K, Hamamura K, Furukawa K.
    • Journal Title

      Cancer Res.

      Volume: 71 Pages: 4989-4997

    • DOI

      10.1158/0008-5472.CAN-10-4108

    • Peer Reviewed
  • [Journal Article] Gangliosides are essential in the protection of inflammation and neurodegeneration via maintenance of lipid rafts : elucidation by a series of ganglioside-deficient mutant mice2010

    • Author(s)
      Ohmi Y, Tajima O, Ohkawa Y, Yamauchi Y, Sugiura Y, Furukawa K, Furukawa K.
    • Journal Title

      J Neurochem.

      Volume: 116 Pages: 926-935

    • DOI

      10.1111/j.1471-4159.2010.07067.x

    • Peer Reviewed
  • [Journal Article] GM1/GD1b/GA1 synthase expression results in the reduced cancer phenotypes with modulation of composition and raft-localization of gangliosides in a melanoma cell line2010

    • Author(s)
      Dong Y, Ikeda K, Hamamura K,Zhang Q, Kondo Y, Matsumoto Y, Ohmi Y, Yamauchi Y, Furukawa K, Taguchi R, Furukawa K.
    • Journal Title

      Cancer Sci.

      Volume: 101 Pages: 2039-2047

    • DOI

      10.1111/j.1349-7006.2010.01613.x

    • Peer Reviewed
  • [Journal Article] Ganglioside GD3 enhances adhesion signals and augments malignant properties of melanoma cells by recruiting integrins to glycolipid-enriched microdomains2010

    • Author(s)
      Ohkawa Y, Miyazaki S, Hamamura K, Kambe M, Miyata M,Tajima O, Ohmi Y, Yamauchi Y, Furukawa K, Furukawa K.
    • Journal Title

      J Biol Chem.

      Volume: 285 Pages: 27213-27223

    • DOI

      10.1074/jbc.M109.087791

    • Peer Reviewed
  • [Presentation] Role of mTOR kinase in the lipogenic phenotype of human cancer cells2012

    • Author(s)
      山内 祥生, 五十嵐 政智, 古 川 鋼 一
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡国際会議場, 福岡市
    • Year and Date
      2012-12-16
  • [Presentation] Regulation of cholesterol homeostasis by ABCA1-dependent retrograde sterol transport2012

    • Author(s)
      山内 祥生
    • Organizer
      第7回トランスポーター研究会年会
    • Place of Presentation
      京都大学, 京都市
    • Year and Date
      2012-06-09
  • [Presentation] Miglustat and cyclodextrin promote lysosome-to- plasma membrane transport of disease-associated gangliosides in Niemann-Pick type C cells2012

    • Author(s)
      Yoshio Yamauchi
    • Organizer
      Gordon Research Conference, Glycolipid & Sphingolipid Biology
    • Place of Presentation
      Lucca, Italy
    • Year and Date
      2012-04-24
  • [Presentation] The Niemann- Pick type C protein NPC1 regulates trafficking of disease-associated ganglioside from the lysosome to the plasma membrane2011

    • Author(s)
      Yoshio Yamauchi, Kosuke Yoshida, Ta-Yuan Chang, Keiko Furukawa, Koichi Furukawa
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜, 横浜市
    • Year and Date
      2011-12-14
  • [Presentation] ABCA1, membrane meso-domains, and sterol sensing2011

    • Author(s)
      Yoshio Yamauchi
    • Organizer
      iCeMS Joint International Symposium ABC 2011 in Kyoto
    • Place of Presentation
      京都大学, 京都市
    • Year and Date
      2011-11-16
  • [Presentation] Total analyses on the roles of cancer-associated gangliosides in malignant properties of melanomas2011

    • Author(s)
      Yoshio Yamauchi, Kazunori Hamamura, Yuki Ohkawa, Noboru Hashimoto, Yuhsuke Ohmi, Keiko Furukawa, Koichi Furukawa
    • Organizer
      70th Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      名古屋国際会議場, 名古屋市
    • Year and Date
      2011-10-04
  • [Presentation] Tumor antigen- activated lipogenic pathway is regulated via mTOR signaling : Crucial role of mTOR-SREBP pathway in the integrity of lipid rafts2011

    • Author(s)
      山内 祥生, 古川 圭子, 浜村 和紀, 古川 鋼一
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      国立京都国際会館, 京都市
    • Year and Date
      2011-09-24
  • [Presentation] Positive feedback loop between PI3K-Akt-mTORC1 signaling and the lipogenic pathway boosts Akt signaling : Induction of the lipogenic pathway by a melanoma antigen2011

    • Author(s)
      Yoshio Yamauchi, Keiko Furukawa, Kazunori Hamamura, Koichi Furukawa
    • Organizer
      The 30th Naito Conference on Membrane Dynamics and Lipid Biology [II] : Domains, Droplets and Diseases
    • Place of Presentation
      シャトレーゼガトーキングダムサッポロ, 札幌市
    • Year and Date
      2011-06-30
  • [Presentation] Lysosomal accumulation of disease-associated gangliosides and small molecules that stimulate their lysosome-to-plasma membrane transport in Niemamm-Pick type C cells2010

    • Author(s)
      Yoshio Yamauchi, Kosuke Yoshida, Ta-Yuan Chang, Keiko Furukawa, Koichi Furukawa
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
    • Place of Presentation
      神戸国際会議場, 神戸市
    • Year and Date
      2010-12-07
  • [Presentation] Accumulation of disease-related ganglosides in the late endosome/lysosome and small molecules that stimulates their transport to the plasma membrane in Niemann-Pick type C cells2010

    • Author(s)
      Yoshio Yamauchi, Kosuke Yoshida, Ta-Yuan Chang, Koichi Furukawa
    • Organizer
      GlycoT 2010 Tokyo 7th International Symposium on Glycosyltransferases
    • Place of Presentation
      KFC-Kokusai Fashion Center, 東京都墨田区
    • Year and Date
      2010-07-31

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Published: 2015-06-25  

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