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The mechanism of cellular tumorigenesis by a novel mTOR signaling pathway

Research Project

Project/Area Number 18K07255
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 InstitutionAichi Cancer Center Research Institute

Principal Investigator

Sato Tatsuhiro  愛知県がんセンター(研究所), 分子腫瘍学分野, 主任研究員 (70547893)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsRheb / SmgGDS / mTOR / mTORC1 / 悪性中皮腫 / RHEB
Outline of Final Research Achievements

The mechanism of mTORC1 regulation by SmgGDS was revealed. Further, the phosphorylation sites of two proteins that are directly phosphorylated by mTORC1 were identified.
Analysis of malignant mesothelioma identified changes in the expression of genes involved in the regulation of mTORC1 activity, which were associated with the prognosis of mesothelioma patients. We found that suppression of SmgGDS expression inhibits mTORC1 activity in malignant mesothelioma cells and inhibits tumor growth in vitro and in vivo.

Academic Significance and Societal Importance of the Research Achievements

本研究はmTORC1調節機構の一端を明らかにしている。mTORC1は細胞増殖やオートファジーの制御を通じて生体の多くの機能に関与しており、本研究成果はそれらの分子機序の解明につながると期待できる。また、mTORC1制御機構の破綻はがんをはじめ、種々の疾患と密接に関連しており、これら疾患の分子機序の解明や、悪性中皮腫をはじめとする種々のがんに対する新たな治療戦略の構築が期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (5 results)

All 2021 2019 2018 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (3 results) (of which Invited: 1 results) Remarks (1 results)

  • [Journal Article] Silencing of SmgGDS, a Novel mTORC1 Inducer That Binds to RHEBs, Inhibits Malignant Mesothelioma Cell Proliferation2021

    • Author(s)
      Sato Tatsuhiro、Mukai Satomi、Ikeda Haruna、Mishiro-Sato Emi、Akao Ken、Kobayashi Toshiyuki、Hino Okio、Shimono Wataru、Shibagaki Yoshio、Hattori Seisuke、Sekido Yoshitaka
    • Journal Title

      Molecular Cancer Research

      Volume: - Issue: 5 Pages: 921-931

    • DOI

      10.1158/1541-7786.mcr-20-0637

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] SmgGDSによるRheb-mTORC1シグナル伝達制御と悪性中皮腫がん化への関与2019

    • Author(s)
      佐藤龍洋、向井智美、関戸好孝
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 中皮腫におけるmTORシグナル伝達経路の活性化と新規治療標的因子の探索2019

    • Author(s)
      佐藤龍洋、関戸好孝
    • Organizer
      第1回日本石綿・中皮腫学会学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 悪性中皮腫におけるRheb-SmgGDS-mTORシグナル伝達経路の解析2018

    • Author(s)
      佐藤龍洋、向井智美、関戸好孝
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Remarks] 愛知県がんセンター研究所 分子腫瘍学分野 HP

    • URL

      http://www.pref.aichi.jp/cancer-center/ri/01bumon/03bunshi_shuyo/index.html

    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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