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mTORC1-dependent control of mRNA translation in liver cancer

Research Project

Project/Area Number 21K07102
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 InstitutionKumamoto University

Principal Investigator

Morita Masahiro  熊本大学, 生命資源研究・支援センター, 客員教授 (50549475)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsがん / mRNA翻訳 / mTORC1 / 代謝リプログラミング / 肝臓がん / mTORC1シグナル / ミトコンドリア
Outline of Research at the Start

がん細胞は代謝プログラムを変化させることにより、限られた栄養素を効率的に利用し、タンパク質や脂質・核酸といった細胞の構成成分を盛んに合成している。タンパク質合成はがん細胞において異常に活性化しており、エネルギーを最も消費している。研究代表者は、がん細胞において活性化しているmTORC1シグナル伝達経路が、mRNA翻訳を刺激することによりタンパク質合成および発がんを促進していることを明らかにしてきた。本研究課題では、肝臓がんにおいてmTORC1によるmRNA翻訳とミトコンドリア制御を介したエネルギーバランスの維持機構を明らかにすることにより、新たながんの治療法確立へ貢献することを目的としている。

Outline of Final Research Achievements

This research project aimed to elucidate the molecular mechanisms underlying the impact of obesity on cancer development and progression. We demonstrated that the nutrient-sensing mTORC1 pathway plays a crucial role in maintaining energy balance in cancer cells. Employing polysome profiling and RNA-seq analysis, we identified mRNAs translationally activated in tumors. This analysis led to the proposal of a novel concept, "dynamic changes in disease mRNA translation for protein homeostasis maintenance," which significantly contributed to unraveling the mechanisms of obesity-associated cancer development. During the grant period, we published a corresponding-author paper in Cell Metabolism and co-authored articles in high-impact journals such as Science Advances, Aging Cell, and Hepatology.

Academic Significance and Societal Importance of the Research Achievements

本研究は、肥満ががんの発症・進展に与える影響を分子レベルで解明し、「エネルギーバランス維持のためのmRNA翻訳の動的変化」という新たな概念を提唱することで、肥満関連がんの発症メカニズムを解明した。この成果は、新たな治療標的の創出、早期診断・治療法の開発、予防法の開発、公衆衛生政策の策定など、肥満関連がん対策の様々な側面に貢献することが期待される。更なる研究開発を通じて、肥満関連がんという深刻な課題克服に貢献していくことが重要である。

Report

(2 results)
  • 2023 Final Research Report ( PDF )
  • 2022 Research-status Report
  • Research Products

    (10 results)

All 2023 2022 Other

All Int'l Joint Research (3 results) Journal Article (3 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 3 results) Presentation (3 results) (of which Invited: 3 results) Remarks (1 results)

  • [Int'l Joint Research] McGill University/Queen's University(カナダ)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] Karolinska Institute(スウェーデン)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] University of Texas Health Science/University of Texas Southwestern/Massachusetts Institute of Technology(米国)

    • Related Report
      2022 Research-status Report
  • [Journal Article] Age‐dependent loss of hepatic SIRT1 enhances NLRP3 inflammasome signaling and impairs capacity for liver fibrosis resolution2023

    • Author(s)
      Adjei‐Mosi Jennifer、Sun Qing、Smithson Steven Blake、Shealy Gavyn Lee、Amerineni Krupa Dhruvitha、Liang Zerong、Chen Hanqing、Wang Mei、Ping Qinggong、Han Jingyan、Morita Masahiro、Kamat Amrita、Musi Nicolas、Zang Mengwei
    • Journal Title

      Aging Cell

      Volume: Online Issue: 5 Pages: 13811-13811

    • DOI

      10.1111/acel.13811

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Targeting hepatic serine-arginine protein kinase 2 ameliorates alcohol-associated liver disease by alternative splicing control of lipogenesis2023

    • Author(s)
      Li Guannan、Chen Hanqing、Shen Feng、Smithson Steven Blake、Shealy Gavyn Lee、Ping Qinggong、Liang Zerong、Han Jingyan、Adams Andrew C.、Li Yu、Feng Dechun、Gao Bin、Morita Masahiro、Han Xianlin、Huang Tim H.、Musi Nicolas、Zang Mengwei
    • Journal Title

      Hepatology

      Volume: Publish Ahead of Print Issue: 5 Pages: 1097-1097

    • DOI

      10.1097/hep.0000000000000433

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Deadenylase-dependent mRNA decay of GDF15 and FGF21 orchestrates food intake and energy expenditure2022

    • Author(s)
      Katsumura Sakie、Siddiqui Nadeem、Goldsmith Michael Rock、Cheah Jaime H.、Fujikawa Teppei、Minegishi Genki、Yamagata Atsushi、Yabuki Yukako、Kobayashi Kaoru、Shirouzu Mikako、Inagaki Takeshi、Huang Tim H.-M.、Musi Nicolas、Topisirovic Ivan、Larsson Ola、Morita Masahiro
    • Journal Title

      Cell Metabolism

      Volume: 34 Issue: 4 Pages: 564-580.e8

    • DOI

      10.1016/j.cmet.2022.03.005

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Orchestrating inter-organ communication and treating metabolic syndrome by targeting mRNA decay of hepatokines2022

    • Author(s)
      Masahiro Morita
    • Organizer
      Waseda University
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] mRNA decay of hepatokines orchestrates inter-organ communication to regulate food intake and energy expenditure2022

    • Author(s)
      Masahiro Morita
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] mRNA decay of hepatokines orchestrates inter-organ communication to regulate food intake and energy expenditure2022

    • Author(s)
      Masahiro Morita
    • Organizer
      OIST
    • Related Report
      2022 Research-status Report
    • Invited
  • [Remarks]

    • URL

      https://scholar.google.co.jp/citations?user=yFXA91UAAAAJ&hl=ja

    • Related Report
      2022 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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