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Functional analysis of nicotinamide metabolism in cancer-specific nutrient metabolic pathways

Research Project

Project/Area Number 20K07565
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 InstitutionKanazawa University

Principal Investigator

Ueno Masaya  金沢大学, がん進展制御研究所, 助教 (20334766)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsがん / 代謝 / 薬剤耐性 / ニコチンアミド代謝 / 白血病 / ニコチンアミド / ビタミン代謝 / ビタミン
Outline of Research at the Start

がんは旺盛な増殖能を発揮するが、様々なストレスに抗して生き残る機能も兼ね備えている。このストレス応答には、様々な代謝調節機構が関与しており、がんの根治には、がん特有の代謝調節機構の解明が重要である。研究代表者らはニコチンアミド代謝酵素が、がん細胞の増殖や抗がん剤耐性に関与していることを見出した。本研究では(1)正常およびがん細胞でのニコチンアミド代謝経路の機能解析、(2)がんの増殖および治療抵抗性におけるNNMTの機能解析、(3)ニコチンアミド経路を指標としたニッチ細胞の特定を実施し、がん特異的なニコチンアミド代謝や、がんの増殖・治療抵抗性におけるニコチンアミド代謝酵素の機能を明らかにする。

Outline of Final Research Achievements

Cancer cells convert nutrients into energy and show high proliferative capacity, but they also have the ability to resist stress for survival. Various metabolic regulatory mechanisms are involved in the stress response to anti-cancer treatments, and the development of drugs to cancer requires the elucidation of regulation mechanisms of cancer-specific metabolisms. In this study, we aimed to elucidate cancer-specific metabolisms by understanding the functions of nicotinamide metabolic pathways in cancer survival and anti-cancer drug resistance. Through this study, we identified metabolites from the nicotinamide metabolic pathway that induce or, conversely, suppress therapeutic resistance. It was suggested that cancers acquire therapeutic resistance by regulating the balance of these metabolites.

Academic Significance and Societal Importance of the Research Achievements

がんの根治を目指した治療法の開発には、がん細胞の特性を知り、その制御を司る重要な分子を特定することが必要である。研究代表者らは、がん細胞の代謝調節に着目し研究を進め、ニコチンアミド代謝経路およびその代謝物が抗がん剤耐性に重要であることを明らかにした。これらの知見は、代謝経路の阻害剤と抗がん剤を組み合わせた新たな治療法の確立に貢献することが期待される。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (5 results)

All 2022 2021 2020

All Journal Article (4 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Patent(Industrial Property Rights) (1 results)

  • [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
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 621 Pages: 74-79

    • DOI

      10.1016/j.bbrc.2022.06.089

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Therapeutic advantage of targeting lysosomal membrane integrity supported by lysophagy in malignant glioma2022

    • Author(s)
      Jing Yongwei、Kobayashi Masahiko、Vu Ha Thi、Kasahara Atsuko、Chen Xi、Pham Loc Thi、Kurayoshi Kenta、Tadokoro Yuko、Ueno Masaya、Todo Tomoki、Nakada Mitsutoshi、Hirao Atsushi
    • Journal Title

      Cancer Science

      Volume: 113 Issue: 8 Pages: 2716-2726

    • DOI

      10.1111/cas.15451

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Essential role of autophagy in protecting neonatal haematopoietic stem cells from oxidative stress in a p62-independent manner2021

    • Author(s)
      Nomura Naho、Ito Chiaki、Ooshio Takako、Tadokoro Yuko、Kohno Susumu、Ueno Masaya、Kobayashi Masahiko、Kasahara Atsuko、Takase Yusuke、Kurayoshi Kenta、Si Sha、Takahashi Chiaki、Komatsu Masaaki、Yanagawa Toru、Hirao Atsushi
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 1666-1679

    • DOI

      10.1038/s41598-021-81076-z

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pillar[6]arene acts as a biosensor for quantitative detection of a vitamin metabolite in crude biological samples2020

    • Author(s)
      Ueno Masaya、Tomita Takuya、Arakawa Hiroshi、Kakuta Takahiro、Yamagishi Tada-aki、Terakawa Jumpei、Daikoku Takiko、Horike Shin-ichi、Si Sha、Kurayoshi Kenta、Ito Chiaki、Kasahara Atsuko、Tadokoro Yuko、Kobayashi Masahiko、Fukuwatari Tsutomu、Tamai Ikumi、Hirao Atsushi、Ogoshi Tomoki
    • Journal Title

      Communications Chemistry

      Volume: 3 Issue: 1 Pages: 1-10

    • DOI

      10.1038/s42004-020-00430-w

    • NAID

      120006939157

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Patent(Industrial Property Rights)] 1‐メチルニコチンアミドの測定方法及びニコチンアミド-N-メチル基転移 酵素阻害剤のスクリーニング方法2020

    • Inventor(s)
      平尾敦、生越友樹、上野将也
    • Industrial Property Rights Holder
      平尾敦、生越友樹、上野将也
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-174186
    • Filing Date
      2020
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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