Identification of critical metabolic pathways and metabolites that regulate therapeutic resistance and stemness
Project/Area Number |
19H01033
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Research Category |
Grant-in-Aid for Scientific Research (A)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Medium-sized Section 50:Oncology and related fields
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Research Institution | Kanazawa University |
Principal Investigator |
Hirao Atsushi 金沢大学, がん進展制御研究所, 教授 (90343350)
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Project Period (FY) |
2019-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥45,110,000 (Direct Cost: ¥34,700,000、Indirect Cost: ¥10,410,000)
Fiscal Year 2022: ¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000)
Fiscal Year 2021: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
Fiscal Year 2020: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
Fiscal Year 2019: ¥12,090,000 (Direct Cost: ¥9,300,000、Indirect Cost: ¥2,790,000)
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Keywords | 代謝 / がん / 幹細胞 |
Outline of Research at the Start |
がんの発生や悪性化プロセスにおける幹細胞特性・未分化形質(ステムネス)の獲得は重要な生物学的特徴であり、その制御機構の解明は、がんの本態解明の手掛かりとなる。最近、がん細胞で特異的に産生される代謝物が発がんの原因となり、その阻害が分化誘導を惹起するなど、「代謝とステムネス」の密接な関係が浮き彫りになってきた。本研究では、発がんに寄与する代謝経路やメタボライトの特定、治療抵抗性とステムネスを制御する代謝経路の特定を進め、がんステムネスの獲得・維持機構を明らかにする。
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Outline of Final Research Achievements |
In this study, we aimed to identify metabolic pathways and metabolites that contribute to tumorigenesis and regulate therapeutic resistance and stemness. We found that metabolic regulation by lysosomes plays an important role in malignant properties in leukemia and brain tumors. We found that lysosome activity was closely linked to chromatin regulation, suggesting that it contributes to fate determination. The findings also contribute to the development of novel therapeutic strategies targeting lysosomes. Further investigation based on this study will provide an effective opening for elucidating the true nature of cancer.
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Academic Significance and Societal Importance of the Research Achievements |
昨今、がんの代謝制御の重要性が認知され、国内外で精力的に研究が進められている。特に、代謝酵素は治療標的としての創薬に直結する可能性が高いため、産業的な発展を念頭に精力的に研究が推進されている。今回の研究では、このような代謝制御ががん細胞の運命決定に寄与していることを明らかにできた。今後、代謝経路の同定、新規のメタボライトの同定とその制御機構、代謝物によるがんの不均一生という観点での研究を展開することで、新規がん診断・治療薬の開発につながると考えられた。
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Report
(6 results)
Research Products
(31 results)
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[Journal Article] RHEB is a potential therapeutic target in T cell acute lymphoblastic leukemia2022
Author(s)
Pham Loc Thi、Peng Hui、Ueno Masaya、Kohno Susumu、Kasada Atuso、Hosomichi Kazuyoshi、Sato Takehiro、Kurayoshi Kenta、Kobayashi Masahiko、Tadokoro Yuko、Kasahara Atsuko、Shoulkamy Mahmoud I.、Xiao Bo、Worley Paul F.、Takahashi Chiaki、Tajima Atsushi、Hirao Atsushi
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Journal Title
Biochemical and Biophysical Research Communications
Volume: 621
Pages: 74-79
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Intracellular metabolic adaptation of intraepithelial CD4+CD8αα+ T lymphocytes2022
Author(s)
Harada Y, Sujino T, Miyamoto K, Nomura E, Yoshimatsu Y, Tanemoto S, Umeda S, Ono K, Mikami Y, Nakamoto N, Takabayashi K, Hosoe N, Ogata H, Ikenoue T, Hirao A, Kubota Y, Kanai T.
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Journal Title
iScience
Volume: 25
Issue: 4
Pages: 104021-104021
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] CDK8 maintains stemness and tumorigenicity of glioma stem cells by regulating the c-MYC pathway2021
Author(s)
Fukasawa K, Kadota T, Horie T, Tokumura K, Terada R, Kitaguchi Y, Park G, Ochiai S, Iwahashi S, Okayama Y, Hiraiwa M, Yamada T, Iezaki T, Kaneda K, Yamamoto M, Kitao T, Shirahase H, Hazawa M, Wong RW, Todo T, Hirao A, Hinoi E.
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Journal Title
Oncogene
Volume: ー
Issue: 15
Pages: 2803-2815
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Identification of a novel arthritis-associated osteoclast precursor macrophage regulated by FoxM1.2019
Author(s)
Hasegawa T, Kikuta J, Sudo T, Matsuura Y, Matsui T, Simmons S, Ebina K, Hirao M, Okuzaki D, Yoshida Y, Hirao A, Kalinichenko VV, Yamaoka K, Takeuchi T, Ishii M.
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Journal Title
Nat Immunol.
Volume: 20
Issue: 12
Pages: 1631-1643
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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