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Regulation of aging and cancer progression by targeting mTOR nutrient signaling

Research Project

Project/Area Number 17K19596
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Tumor biology and related fields
Research InstitutionOsaka University

Principal Investigator

Masato Okada  大阪大学, 微生物病研究所, 教授 (10177058)

Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2017: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Keywords栄養シグナル / 老化 / がん化 / 健康寿命 / mTOR / シグナル伝達 / 代謝制御 / がん進展 / リソソーム / 細胞老化 / がん / 阻害剤 / FRET / BRET / 癌
Outline of Final Research Achievements

To suppress tumor progression, it is important to control nutrient signaling that supports active growth and proliferation of cancer cells. In this study, to develop new anti-cancer and/or anti-aging drugs by targeting the nutrient signaling molecule mTORC1, which is a master regulator of cell growth and cellular metabolism, we elucidated the regulatory mechanisms of mTORC1 based on the molecular structures of its regulators and explored new regulatory surfaces that can be accessed by therapeutic drugs.

Academic Significance and Societal Importance of the Research Achievements

本邦では、高齢化が進むにつれて医療費などが増大するなど様々な社会問題が生じ、健康寿命の延伸が重要課題となってきている。また、健康寿命の延伸を阻む重大な要因として「がん」の罹患率も上昇し続けている。がんの発症は老化と密接に関わることから、それを抑止するためには、細胞の栄養状態に応じて代謝や細胞増殖、ひいては老化や寿命を調節するシグナル分子をコントロールすることが重要となる。本研究では、栄養シグナル分子mTORの調節機構を分子レベルで解析し、その働きを抑制する新規薬剤の標的候補部位を明らかにした。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (15 results)

All 2019 2018 2017

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (9 results) (of which Int'l Joint Research: 1 results,  Invited: 5 results)

  • [Journal Article] Src mediates TGF-β-induced intraocular pressure elevation in glaucoma.2019

    • Author(s)
      Tsukamoto T, Kajiwara K, Nada S, Okada M
    • Journal Title

      J Cell Physiol.

      Volume: 234 Pages: 1730-1744

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Roles of Lamtor1 in Macrophages, CD4+ T-cells, and Regulatory T-cells.2018

    • Author(s)
      Kimura T, Kumanogoh A, Okada M
    • Journal Title

      Critical reviews in immunology

      Volume: 38 Issue: 5 Pages: 403-414

    • DOI

      10.1615/critrevimmunol.2018028252

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rheb localized on the Golgi membrane activates lysosome-localized mTORC1 at the Golgi lysosome contact site2018

    • Author(s)
      Feike Hao, Kazuhiko Kondo, Takashi Itoh, Sumiko Ikari, Shigeyuki Nada, Masato Okada, Takeshi Noda
    • Journal Title

      J cell Science

      Volume: 131 Issue: 3 Pages: 208017-208017

    • DOI

      10.1242/jcs.208017

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lysosomal Protein Lamtor1 Controls Innate Immune Responses via Nuclear Translocation of Transcription Factor EB.2018

    • Author(s)
      Hayama Y, Kimura T, Takeda Y, Nada S, Koyama S, Takamatsu H, Kang S, Ito D, Maeda Y, Nishide M, Nojima S, Sarashina-Kida H, Hosokawa T, Kinehara Y, Kato Y, Nakatani T, Nakanishi Y, Tsuda T, Koba T, Okada M, Kumanogoh A.
    • Journal Title

      J Immunol.

      Volume: 200 Issue: 11 Pages: 3790-3800

    • DOI

      10.4049/jimmunol.1701283

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural basis for the assembly of the Ragulator-Rag GTPase complex.2017

    • Author(s)
      Yonehara R, Nada S, Nakai T, Nakai M, Kitamura A, Ogawa A, Nakatsumi H, Nakayama KI, Li S, Standley DM, Yamashita E, Nakagawa A, Okada M.
    • Journal Title

      Nat Commun.

      Volume: 8 Issue: 1 Pages: 1625-1625

    • DOI

      10.1038/s41467-017-01762-3

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Lamtor1 Is Critically Required for CD4+ T Cell Proliferation and Regulatory T Cell Suppressive Function.2017

    • Author(s)
      Hosokawa T, Kimura T, Nada S, Okuno T, Ito D, Kang S, Nojima S, Yamashita K, Nakatani T, Hayama Y, Kato Y, Kinehara Y, Nishide M, Mikami N, Koyama S, Takamatsu H, Okuzaki D, Ohkura N, Sakaguchi S, Okada M, Kumanogoh A.
    • Journal Title

      J Immunol.

      Volume: 199 Issue: 6 Pages: 2008-2019

    • DOI

      10.4049/jimmunol.1700157

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Molecular basis for the regulation of mTORC1 nutrient signaling2019

    • Author(s)
      岡田雅人
    • Organizer
      「数理シグナル」第1回国際シンポジウム
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] がん進展制御におけるSrcおよびmTORシグナルの役割2019

    • Author(s)
      岡田雅人
    • Organizer
      金沢大学がん進展制御研究所セミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] がん発展におけるSrcチロシンキナーゼの立ち位置2018

    • Author(s)
      岡田雅人
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] リソソーム膜上でのmTORC1栄養シグナルの制御機構2018

    • Author(s)
      岡田雅人
    • Organizer
      大阪大学蛋白質研究所セミナー
    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Invited
  • [Presentation] Srcの時空間的制御によるがん細胞の運命決定2018

    • Author(s)
      梶原健太郎、Ping-Kuan Chen、岡田雅人
    • Organizer
      第41回日本分子生物学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] The structural basis for the assembly of the Ragulator-RagGTPase complex2018

    • Author(s)
      中井 昌弘、米原 涼、名田 茂之、中井 友和、中川 敦史、岡田 雅人
    • Organizer
      新学術領域研究「数理シグナル」第2回公開シンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] mTORC1栄養シグナル制御の分子基盤解析2017

    • Author(s)
      岡田雅人
    • Organizer
      新学術領域研究「数理シグナル」領域推進会議
    • Related Report
      2017 Research-status Report
  • [Presentation] リソソーム膜上におけるmTORC1シグナルの制御機構2017

    • Author(s)
      岡田雅人
    • Organizer
      第四回バイオシグナル研究会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Ragulatorの構造とRagとの複合体形成機構2017

    • Author(s)
      名田 茂之、米原 涼、中井 昌弘、北村 彩佳、小川 輝、山下 栄樹、中川 敦史、岡田 雅人
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Research-status Report

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Published: 2017-07-21   Modified: 2020-03-30  

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