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Mechanism and significance of GTP metabolic switch in brain tumors

Research Project

Project/Area Number 18K07233
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 50010:Tumor biology-related
Research InstitutionTokyo Medical and Dental University (2019-2020)
Hiroshima University (2018)

Principal Investigator

Kofuji Satoshi  東京医科歯科大学, 難治疾患研究所, 講師 (00508153)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords脳腫瘍 / グアノシン三リン酸 / 核小体 / 代謝 / IMPDH / MYC / GTP / リボソームRNA / トランスファーRNA / GTP代謝 / 神経膠芽腫
Outline of Final Research Achievements

In this study, we investigated the significance of nucleotide metabolism in glioblastoma, a malignant brain tumor. Inhibition of the synthesis of guanosine triphosphate suppressed proliferation and tumorigenesis of glioblastoma cells. Mechanistically, the synthesis of ribosomes, which is a machinery of protein synthesis, was directly connected to guanosine triphosphate metabolism. Moreover, inhibition of guanosine triphosphate metabolism also caused nucleolar stress.

Academic Significance and Societal Importance of the Research Achievements

本研究結果は、グアノシン三リン酸代謝が神経膠芽腫の治療における新たな標的となりうることを示唆している。グアノシン三リン酸代謝は神経膠芽腫細胞特異的に亢進している代謝であり、この代謝の阻害は正常細胞への影響が少ない。そのため、副作用の少ない治療法の確立へとつながることが期待できる。また、がん細胞におけるグアノシン三リン酸代謝と核小体活性のつながりを見出したという点で学術的に意義深い。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (21 results)

All 2020 2019 2018 Other

All Int'l Joint Research (3 results) Journal Article (5 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (12 results) (of which Invited: 1 results) Remarks (1 results)

  • [Int'l Joint Research] University of Cincinnati(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] University of Cincinnati(米国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] University of Cincinnati(米国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] GTP metabolic reprogramming by IMPDH2: unlocking cancer cells’ fuelling mechanism2020

    • Author(s)
      Kofuji Satoshi、Sasaki Atsuo T
    • Journal Title

      The Journal of Biochemistry

      Volume: 168 Issue: 4 Pages: 319-328

    • DOI

      10.1093/jb/mvaa085

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] IMP dehydrogenase-2 Drives Aberrant Nucleolar Activity and Promotes Tumorigenesis in Glioblastoma2019

    • Author(s)
      Kofuji S, Hirayama A, Eberhardt AO, Kawaguchi R, Sakamoto N, Kitahara S, Wolfe K, Lange L, Onishi N, Uematsu M, Saya H, Soga T, Grummt I, Bierhoff H, Sasaki AT.
    • Journal Title

      Nat Cell Biol

      Volume: 21 Issue: 8 Pages: 1003-1014

    • DOI

      10.1038/s41556-019-0363-9

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dynamic compartmentalization of purine nucleotide metabolic enzymes at leading edge in highly motile renal cell carcinoma.2019

    • Author(s)
      Wolfe K, Kofuji S, Yoshino H, Sasaki M, Okumura K, Sasaki AT
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 516 Issue: 1 Pages: 50-56

    • DOI

      10.1016/j.bbrc.2019.05.190

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Anti-Tumor Potential of IMP Dehydrogenase Inhibitors: A Century-Long Story.2019

    • Author(s)
      Naffouje R, Grover P, Yu H, Sendilnathan A, Wolfe K, Majd N, Smith EP, Takeuchi K, Senda T, Kofuji S, Sasaki AT
    • Journal Title

      Cancers (Basel)

      Volume: 11 Issue: 9 Pages: 1346-1346

    • DOI

      10.3390/cancers11091346

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Lysophosphatidylinositol‐acyltransferase‐1 is involved in cytosolic Ca2+ oscillations in macrophages2019

    • Author(s)
      Takemasu Shinya、Ito Masaki、Morioka Shin、Nigorikawa Kiyomi、Kofuji Satoshi、Takasuga Shunsuke、Eguchi Satoshi、Nakanishi Hiroki、Matsuoka Isao、Sasaki Junko、Sasaki Takehiko、Hazeki Kaoru
    • Journal Title

      Genes to Cells

      Volume: - Issue: 5 Pages: 1-11

    • DOI

      10.1111/gtc.12681

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] グアニンヌクレオチド代謝リプログラミングが制御する腫瘍形成のメカニズム2020

    • Author(s)
      小藤智史
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 物質代謝異常によるがん発症機構の解明2020

    • Author(s)
      小藤智史
    • Organizer
      第1回 細胞死コロキアム
    • Related Report
      2020 Annual Research Report
  • [Presentation] 脳腫瘍における核小体の活性化制御とGTP代謝リプログラミング2020

    • Author(s)
      小藤智史、佐々木敦朗
    • Organizer
      第140年会日本薬学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 神経膠芽腫における de novo GTP 合成経路の意義2019

    • Author(s)
      小藤智史
    • Organizer
      第 18 回生命科学研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] GTP-metabolic reprograming that regulates the nucleolar activity and tumorigenesis2019

    • Author(s)
      Satoshi Kofuji, Atsuo Sasaki
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 神経膠芽腫における GTP 代謝の役割2018

    • Author(s)
      小藤智史
    • Organizer
      第 17 回生命科学研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] 神経膠芽腫と GTP 代謝2018

    • Author(s)
      小藤智史
    • Organizer
      第1回 HiHA&HIRAKU 若手研究者 Workshop
    • Related Report
      2018 Research-status Report
  • [Presentation] リゾホスファチジルイノシトールアシル基転移酵素 ( LPIAT1 ) は G タンパク質依存性 Ca2+ 流入に寄与する2018

    • Author(s)
      竹増真也、濁川清美、小藤智史、櫨木薫
    • Organizer
      第57回日本薬学会・日本薬剤師会・日本病院薬剤師会 中国四国支部学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] イノシトールリン脂質5位リン酸化酵素 PIKfyve の食胞成熟における役割2018

    • Author(s)
      鶴海剛、濁川清美、小藤智史、櫨木薫
    • Organizer
      第57回日本薬学会・日本薬剤師会・日本病院薬剤師会 中国四国支部学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] クラス II 型 PI3 キナーゼによるファゴサイトーシスの制御2018

    • Author(s)
      川波知裕、濁川清美、小藤智史、櫨木薫
    • Organizer
      第57回日本薬学会・日本薬剤師会・日本病院薬剤師会 中国四国支部学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] TMEM55 によるマクロファージスカベンジャー受容体の発現制御2018

    • Author(s)
      春名勇希、濁川清美、小藤智史、櫨木薫
    • Organizer
      第57回日本薬学会・日本薬剤師会・日本病院薬剤師会 中国四国支部学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 神経膠芽腫における GTP 代謝亢進の意義2018

    • Author(s)
      小藤智史、佐々木敦朗
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Remarks] 120年の謎・がんの「鬼の目」を閉じるには? -がんのエネルギー産生と配分の仕組みを発見-

    • URL

      https://www.hiroshima-u.ac.jp/news/52594

    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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