Mechanism and significance of GTP metabolic switch in brain tumors
| Project/Area Number |
18K07233
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 50010:Tumor biology-related
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| Research Institution | Tokyo Medical and Dental University (2019-2020)
Hiroshima University (2018) |
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Principal Investigator |
Kofuji Satoshi 東京医科歯科大学, 難治疾患研究所, 講師 (00508153)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| 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)
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| 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.
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| 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。
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Report
(4 results)
Research Products
(21 results)
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[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.
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Journal Title
Nat Cell Biol
Volume: 21
Issue: 8
Pages: 1003-1014
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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
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Journal Title
Cancers (Basel)
Volume: 11
Issue: 9
Pages: 1346-1346
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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