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Integrative understanding of linkage between molecular structures and functions of glycosphingolipids in signal regulation

Research Project

Project/Area Number 15H04696
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

FURUKAWA Koichi  中部大学, 生命健康科学部, 教授 (80211530)

Co-Investigator(Kenkyū-buntansha) 大海 雄介  中部大学, 生命健康科学部, 助手 (10584758)
山内 祥生  名古屋大学, 医学系研究科, 講師 (00444878)
Co-Investigator(Renkei-kenkyūsha) OHKAWA Yuki  中部大学, 生命健康科学部, 研究員 (40723896)
ANDO Hiromune  岐阜大学, 応用生物科学部, 教授 (20372518)
SUZUKI Kenichi  京都大学, 工学部, 准教授 (50423059)
IKEDA Kazutaka  独立行政法人理化学研究所, 生命医科学研究センター, 上級研究員 (10466732)
HONKE Koichi  高知大学, 医歯学系, 教授 (80190263)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2017: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2016: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2015: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywordsシグレック / スフィンゴ糖脂質 / セラミド / 脂肪酸 / ガングリオシド / 脂質修飾 / シグナル制御 / 糖鎖 / シグナル伝達 / 癌 / 生体分子 / 糖脂質 / ノックアウト / 脂質 / シグナル
Outline of Final Research Achievements

To investigate the mechanisms for signal regulation by glycosphingolipids expressed on the cell surface, chemical structures of whole molecules of glycolipids including sugar moieties and lipid portions were analyzed. Using sugar-remodeling cancer cells and EMARS/MS, we identified membrane molecules that associate with glycolipids, and verified that these molecules specifically bind with glycolipids, and enhance malignant properties of cancer cells. On the other hand, to clarify the involvement of lipid portions in the signal regulation by glycolipids, we performed knockout of DES2 that hydroxylates long chain base-C4 using GD3-expressing colon cancer, DLD-1, and demonstrated the recovery of the reactivity with Siglec-7. We also performed knockout of FA2H that exerts hydroxylation of fatty acid C2, and verified that binding of Siglec-7 is disturbed by hydroxylation of lipid portions. Furthermore, we observed that the sensitivity of cells to NK was increased in the knockout cells.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (38 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (11 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 11 results,  Open Access: 7 results,  Acknowledgement Compliant: 5 results) Presentation (25 results) (of which Int'l Joint Research: 2 results,  Invited: 5 results) Book (1 results)

  • [Int'l Joint Research] Dundee University/Glasgow University(英国)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Inflammatory reactions in microenviron- ments, leading to melanomagenesis2018

    • Author(s)
      Koichi Furukawa, Maiko Miyata, Mariko Kambe, Rika Takeuchi, Robiul H. Bhuiyan, Pu Zhang, Yuhsuke Ohmi, Keiko Furukawa
    • Journal Title

      J. Clin. Cell. Immunol.

      Volume: 5:508 Issue: 03 Pages: 1-3

    • DOI

      10.4172/2155-9899.1000508

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ASC amino acid transporter 2, defined by enzyme-mediated activation of radical sources, enhances malignancy of GD2-positive small-cell lung cancer.2018

    • Author(s)
      Nobutoshi Esaki, Yuki Ohkawa, Noboru Hashimoto, Yuhsuke Tsuda, Yuhsuke Ohmi, Robiul H. Bhuiyan, Norihiro Kotani, Koichi Honke, Atsushi Enomoto, Masahide Takahashi, Keiko Furukawa, Koichi Furukawa.
    • Journal Title

      Cancer sci.

      Volume: 109 Issue: 1 Pages: 141-153

    • DOI

      10.1111/cas.13448

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glycosylation is involved in malignant properties of cancer cells2017

    • Author(s)
      Kazunori Hamamura and Koichi Furukawa
    • Journal Title

      Cancer Translational Medicine

      Volume: 3 Issue: 6 Pages: 209-213

    • DOI

      10.4103/ctm.ctm_28_17

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glycolipids: Essential regulator of neuro-inflammation, metabolism and gliomagenesis.2017

    • Author(s)
      Koichi Furukawa, Yuhsuke Ohmi, Shuting Ji, Pu Zhang, Robiul H. Bhuiyan, Yuki Ohkawa, Orie Tajima, Noboru Hashimoto, Keiko Furukawa
    • Journal Title

      Biochim. Biophys. Acta

      Volume: 1861 Issue: 10 Pages: 2479-2484

    • DOI

      10.1016/j.bbagen.2017.06.007

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of monoclonal antibodies reactive with alpha-series ganglliosides by immunization of complex ganglioside-deficient mice2016

    • Author(s)
      Bhuiyan RH, Yuji Kondo, Noriyo Tokuda, Ryota Mori, Keiko Furukawa, Koichi Furukawa
    • Journal Title

      Glycobiology

      Volume: 26 Pages: 984-998

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Immunization of A4galt-deficient mice with glycosphingolipids from renal cell cancers resulted in the generation of anti-sulfoglycolipid monoclonal antibodies2016

    • Author(s)
      Ando R, Tokuda N, Yamamoto T, Ikeda K, Hashimoto N, Taguchi R, Fan X, Furukawa K, Niimura Y, Suzuki A, Goto M, Furukawa K.
    • Journal Title

      Glycoconj. J.

      Volume: 33 Issue: 2 Pages: 169-180

    • DOI

      10.1007/s10719-016-9654-6

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] b-series gangliosides crucially regulate leptin secretion in adipose tissues.2015

    • Author(s)
      Ji S., Ohkawa Y., Tokizane K., Ohmi Y., Banno R., Furukawa K., Kiyama H. and Furukawa K.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 459 Issue: 2 Pages: 189-195

    • DOI

      10.1016/j.bbrc.2015.01.143

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Proteasome inhibitors prevent cell death and prolong survival of mice challenged by Shiga toxin2015

    • Author(s)
      Takayuki Hattori, Miho Watanabe-Takahashi, Nobumichi Ohoka, Takashi Hamabata, Koichi Furukawa, Kiyotaka Nishikawa, and Mikihiko Naito
    • Journal Title

      FEBS Open Bio

      Volume: 5 Issue: 1 Pages: 605-614

    • DOI

      10.1016/j.fob.2015.06.005

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Ganglioside GD3 enhances invasiveness via Yes activation by forming a complex of GD3/PDGFRα/Yes in gliomas2015

    • Author(s)
      Yuki Ohkawa, Hiroyuki Momota, Akira Kato, Noboru Hashimoto, Yuhsuke Tsuda, Norihiro Kotani, Koichi Honke, Akio Suzumura, Keiko Furukawa, Yuhsuke Ohmi, Atsushi Natsume, Toshihiko Wakabayashi and *Furukawa K
    • Journal Title

      J. Biol. Chem.

      Volume: 290 Issue: 32 Pages: 16043-16058

    • DOI

      10.1074/jbc.m115.708834

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Regulatory function of glycosphingolipids in the inflammation and degeneration.2015

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

      Arch Biochem Biophys

      Volume: 571 Pages: 58-65

    • DOI

      10.1016/j.abb.2015.02.007

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Deficiency in the Lipid Exporter ABCA1 Impairs Retrograde Sterol Movement and Disrupts Sterol Sensing at the Endoplasmic Reticulum2015

    • Author(s)
      Yamauchi Y, Iwamoto N, Rogers MA, Abe-Dohmae S, Fujimoto T, Chang CC, Ishigami M, Kishimoto T, Kobayashi T, Ueda K, Furukawa K, Chang TY, Yokoyama S.
    • Journal Title

      J Biol Chem

      Volume: 290 Issue: 39 Pages: 23464-23477

    • DOI

      10.1074/jbc.m115.662668

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] シアル酸認識レクチン シグレック7による糖脂質認識の特異性の解析2018

    • Author(s)
      古川鋼一、橋本 登、山本朗仁、Paul Crocker、大海雄介、Robiul H. Bhuiyan, 古川圭子
    • Organizer
      糖鎖免疫Glyco-immunology 2018
    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
  • [Presentation] Regulation of inflammation and malignant tumors by glycosylation2017

    • Author(s)
      Koichi Furukawa
    • Organizer
      Invited Seminar at Academia Sinica, GlycoMedicine Seminar, Taipei
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Regulation of cell signaling by ganglioside GD3/GD2 in gliomas2017

    • Author(s)
      Koichi Furukawa, Yuki Ohkawa, Kei Kaneko, Noboru Hashimoto, Zhang Pu, Robiul H. Bhuiyan, Yuhsuke Ohmi, Keiko Furukawa
    • Organizer
      GLYCO XXIV
    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ガングリオシドGD2 は中性アミノ酸トランスポーターASCT2と協調的に働き小細胞肺がんの悪性形質を亢進させる2017

    • Author(s)
      江崎 寛季、大川 祐樹、橋本 登、津田 祐介、大海 祐介、ブイヤ ロビウル、古谷 典弘、本家 孝一、榎本 篤、高橋 雅英、古川 圭子、古川 鋼一
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
  • [Presentation] Roles of asialo-series ganglioside GD1alpha in human cancer cell lines2017

    • Author(s)
      Robiul H. Bhuiyan, Yuji Kondo, Yuki Ohkawa, Yuhsuke Ohmi, Pu Zhang, Tetsuya Okajima,Keiko Furukawa, Koichi Furukawa
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
  • [Presentation] ガングリオシドGD3/GD2はヒト由来神経膠腫U251細胞の悪性形質を増強する2017

    • Author(s)
      張璞、岩沢 太司、大川 裕樹、RH Bhuiyan、百田 洋之、若林俊彦、大海 雄介、岡島 徹也、古川 圭子、古川 鋼一
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
  • [Presentation] グリア細胞上の脂質ラフトにおけるガングリオシドの役割2017

    • Author(s)
      大海 雄介、大川 祐樹、張 僕、小林 伊織、小谷 典弘、本家 孝一、古川 圭子、河原 敏男、古川 鋼一
    • Organizer
      生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
  • [Presentation] Regulation of inflammation and malignant tumors by glycosylation2017

    • Author(s)
      Koichi Furukawa:
    • Organizer
      Invited Seminar at Academia Sinica, GlycoMedicine Seminar, Taipei
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] グリオシドGD3によるグリオーマの腫瘍微小環境の制御機構2017

    • Author(s)
      張 璞、大川 裕樹、加藤 彰、小峯 起、百田 洋之、Robiul Bhuiyan、大海 雄介、古川 圭子、若林 俊彦、岡島 徹也、山中 宏二、古川 鋼一
    • Organizer
      生命科学系学会合同年次大会
    • Related Report
      2016 Annual Research Report
  • [Presentation] Roles of ganglioside GD1α in human cancer cells2017

    • Author(s)
      Robiul Bhuiyan、Yuji Kondo、Yuki Ohkawa、Yuhsuke Ohmi、Pu Zhang、Keiko Furukawa、Tetsuya Okajima、Koichi Furukawa
    • Organizer
      生命科学系学会合同年次大会
    • Related Report
      2016 Annual Research Report
  • [Presentation] 癌関連スフィンゴ糖脂質による細胞動態の制御:蛍光標識糖脂質によるタイムラプス解析2017

    • Author(s)
      古川 圭子、神戸 真理子、大川 祐樹、大海 雄介、竹内 理香、田島 織絵、安藤 弘宗、古川 鋼一
    • Organizer
      生命科学系学会合同年次大会
    • Related Report
      2016 Annual Research Report
  • [Presentation] 糖脂質糖鎖によるシグナルの制御のメカニズム2015

    • Author(s)
      古川鋼一、大川祐樹、大海雄介、橋本登、古川圭子
    • Organizer
      第38回日本分子生物学会年会、第88回日本生化学会大会
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] Functional analysis of GD2associated molecules identified by EMARS in lung cancer2015

    • Author(s)
      Nobutosi Esaki, Yuki Ohkawa, Yusuke Tuda, Kei Kaneko, Yusuke Ohmi, Noboru Hashimoto, Norihiro Kotani, Koichi Honke, Keiko Furukawa, Koichi Furukawa
    • Organizer
      第38回日本分子生物学会年会、第88回日本生化学会大会
    • Place of Presentation
      神戸国際展示場(兵庫県神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] TLC-LESA-QTRAP6500によるSiglec-7特異的認識gangliosde GD3の構造解析2015

    • Author(s)
      橋本登、伊藤静香、池田和貴、土田明子、Paul R .Crocker,古川圭子、田口良、古川鋼一
    • Organizer
      第38回日本分子生物学会年会、第88回日本生化学会大会
    • Place of Presentation
      神戸国際展示場(兵庫県神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] ABCトランスポーターABCA1はダイナミン依存症エンドサイトーシスを介したステロー ル逆行輸送を調整する2015

    • Author(s)
      山内祥、岩本紀之、Maximilian A Rogers,どう前純子、藤本豊士、Catherine C.Y.Chang,石神正登、岩本拓磨、小林俊秀、植田和光、古川鋼一、Ta-Yuan Chag,横山信治
    • Organizer
      第38回日本分子生物学会年会、第88回日本生化学会大会
    • Place of Presentation
      神戸国際展示場(兵庫県神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] 皮膚微小環境におけるメラノサイトの糖鎖合成酵素遺伝子の発現調節2015

    • Author(s)
      竹内理香,宮田麻衣子,田島織絵,神戸真理子,古川鋼一 ,古川圭子
    • Organizer
      第38回日本分子生物学会年会、第88回日本生化学会大会
    • Place of Presentation
      神戸国際展示場(兵庫県神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] ヒトmelanoma細胞におけるNeogenin細胞内ドメイン(NelCD)標的遺伝子の同定2015

    • Author(s)
      金子 慶、大川祐樹、橋本 登、大海雄介、山内祥生、岡島徹也、小谷典弘、本家孝一、古川圭子、古川鋼一
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] 癌関連連鎖との協同作用により癌形質を発現する分子群の同定と作用機構2015

    • Author(s)
      古川鋼一,大川祐樹、橋本登、金子慶、小谷典弘、本家孝一、大海雄介、古川圭子
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 肺がん細胞特異的に発現する酸性糖脂質抗原GD2と強調的な分子の同定と機能解析2015

    • Author(s)
      江崎寛季、大川祐樹、橋本登、津田祐介、金子慶、大海雄介、古谷典弘、本家孝一、古川圭子、古川鋼一
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] NK細胞上Siglec-7を介したシアル酸含有O型糖鎖による癌免疫監視からの逃避機構2015

    • Author(s)
      橋本登、土田明子、高野舞子、古川圭子、古川鋼一
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] Expression and roles of asialo-series gangliosides in human cancer cell lines2015

    • Author(s)
      Robiul H .Bhuiyan,Yuji Kondo,Tokiaki,Yamaguti,Noriyo Tokuda,Yuki ohkawa,Yuhsuke Ohmi,Yoshio Yamauchi,Keiko Furukawa,Tetsuya Okajima,Koichi Furukawa
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] Novel functions and mechanisms of complex carbohydrates elucidated by glycosyltransferase gene knockout2015

    • Author(s)
      Koichi Furukawa
    • Organizer
      GLYCO23 (第23回国際糖鎖学会
    • Place of Presentation
      スプリット、クロアチア
    • Year and Date
      2015-09-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Neogenin 細胞内領域(NelCD)はGD3発現メラノーマにおいて、癌悪性形質亢進に関与する2015

    • Author(s)
      金子慶、大川祐樹,橋本登、大海雄介、山内祥生、岡島徹也、小谷典弘、本屋孝一、古川圭子、古川鋼
    • Organizer
      第34回日本糖質学会年会
    • Place of Presentation
      東京大学安田講堂(東京都)
    • Year and Date
      2015-07-31
    • Related Report
      2015 Annual Research Report
  • [Presentation] Siiglec-7の結合特異性におけるガングリオシドGD3の分子種解析2015

    • Author(s)
      橋本 登、伊藤静香、池田和貴、土田明子、Paul R.Croker、古川圭子、田口良、古川鋼一
    • Organizer
      第34回日本糖質学会年会
    • Place of Presentation
      東京大学安田講堂(東京都)
    • Year and Date
      2015-07-31
    • Related Report
      2015 Annual Research Report
  • [Presentation] ガングリオシドGD3はグリオーマの進展を促進する2015

    • Author(s)
      大川祐樹、百田洋介、加藤 彰、橋本 登、津田祐介、古川圭子、大海雄介、夏目敦至、若林俊彦、古川鋼一
    • Organizer
      第34回日本糖質学会年会
    • Place of Presentation
      東京大学安田講堂(東京都)
    • Year and Date
      2015-07-31
    • Related Report
      2015 Annual Research Report
  • [Book] Sugar Chains2015

    • Author(s)
      Koichi Furukawa, Yasuyuki Matsumoto, Qing Zhang, and Keiko Furukawa
    • Publisher
      Springer
    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2022-08-29  

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