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Molecular mechanisms and physiological function of amino acid endocytosis

Research Project

Project/Area Number 18K06018
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 42030:Animal life science-related
Research InstitutionYamaguchi University

Principal Investigator

Shibutani Shusaku  山口大学, 共同獣医学部, 准教授 (20534473)

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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsエンドサイトーシス / アミノ酸 / ダイナミン / 栄養シグナル / mTORC1 / シグナル伝達
Outline of Final Research Achievements

mTORC1 is a major metabolic signaling complex that activates cellular biosynthesis. In this study, we found that endocytosis inhibitors suppressed cell proliferation and mTORC1 activity in various tumor-derived cell lines. It was also confirmed that endocytosis inhibitors increased the number of S-phase cells and induced apoptosis in a tumor-specific manner.
On the other hand, it has been reported that endocytosis activity increases during amino acid starvation, which is thought to be a mechanism to ensure that cells obtain necessary amino acids. Experiments using dynamin-1/2/3 triple knockout cells revealed that dynamin is involved in this phenomenon.

Academic Significance and Societal Importance of the Research Achievements

本研究により、がん細胞に対するエンドサイトーシス阻害剤の細胞増殖抑制作用と、がん細胞にとって重要なアミノ酸確保経路であるエンドサイトーシスの、より詳細なメカニズムが明らかとなった。エンドサイトーシス阻害剤は細胞の栄養取り込み阻害剤として働き、本研究で示されたように栄養要求性の高いがん細胞への対抗するための手段として有効である可能性がある。さらに、エンドサイトーシス活性の調節により適度な栄養取り込みの抑制が実現できれば、過栄養によって引き起こされる肥満や生活習慣病(糖尿病、高血圧、脂質異常症など)の治療薬・予防薬として有効である可能性がある。

Report

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

    (12 results)

All 2021 2020 2019

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 1 results) Presentation (6 results) (of which Invited: 1 results)

  • [Journal Article] Protein phosphatase 6 dissociates the Beclin 1/Vps34 complex and inhibits autophagy2021

    • Author(s)
      Fujiwara Nobuyuki、Shibutani Shusaku、Ohama Takashi、Sato Koichi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 552 Pages: 191-195

    • DOI

      10.1016/j.bbrc.2021.02.136

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Autophagy regulates levels of tumor suppressor enzyme protein phosphatase 6.2020

    • Author(s)
      Nobuyuki Fujiwara, Shusaku Shibutani, Yusuke Sakai, Toshio Watanabe, Issei Kitabayashi, Hiroko Oshima, Masanobu Oshima, Hisashi Hoshida, Rinji Akada, Tatsuya Usui, Takashi Ohama*, Koichi Sato.
    • Journal Title

      Cancer Science

      Volume: 111 Issue: 12 Pages: 4371-4380

    • DOI

      10.1111/cas.14662

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tenovin-6 induces the SIRT-independent cell growth suppression and blocks autophagy flux in canine hemangiosarcoma cell lines2020

    • Author(s)
      Igase Masaya、Fujiki Noriyuki、Shibutani Shusaku、Sakai Hiroki、Noguchi Shunsuke、Nemoto Yuki、Mizuno Takuya
    • Journal Title

      Experimental Cell Research

      Volume: 388 Issue: 1 Pages: 111810-111810

    • DOI

      10.1016/j.yexcr.2019.111810

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Combination Therapy with Reovirus and ATM Inhibitor Enhances Cell Death and Virus Replication in Canine Melanoma2019

    • Author(s)
      Igase Masaya、Shibutani Shusaku、Kurogouchi Yosuke、Fujiki Noriyuki、Hwang Chung Chew、Coffey Matt、Noguchi Shunsuke、Nemoto Yuki、Mizuno Takuya
    • Journal Title

      Molecular Therapy - Oncolytics

      Volume: 15 Pages: 49-59

    • DOI

      10.1016/j.omto.2019.08.003

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Amino acid starvation accelerates replication of Ibaraki virus2019

    • Author(s)
      Onishi Keiko、Shibutani Shusaku、Goto Nanami、Maeda Yuki、Iwata Hiroyuki
    • Journal Title

      Virus Research

      Volume: 260 Pages: 94-101

    • DOI

      10.1016/j.virusres.2018.10.008

    • NAID

      120006813852

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Apoptosis induced by Ibaraki virus does not affect virus replication and cell death in hamster lung HmLu-1 cells2019

    • Author(s)
      TSURUTA Yuya、SHIBUTANI Shusaku、WATANABE Rie、IWATA Hiroyuki
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 81 Issue: 2 Pages: 197-203

    • DOI

      10.1292/jvms.18-0366

    • NAID

      130007592034

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] イバラキウイルスの宿主細胞侵入経路の解析2021

    • Author(s)
      前田祐希、大西慶子、鶴田祐哉、渋谷周作、岩田祐之
    • Organizer
      第163回日本獣医学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] エンドサイトーシス阻害剤によるがん細胞増殖抑制メカニズムの検討2019

    • Author(s)
      末村美希, 渋谷周作, 岩田祐之
    • Organizer
      第162回日本獣医学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] SIRT阻害剤Tenovin-6は犬血管肉腫細胞に対してリソソーム機能障害を誘導する2019

    • Author(s)
      伊賀瀬雅也, 藤木範之, 渋谷周作, 酒井治, 根本有希, 水野拓也
    • Organizer
      第162回日本獣医学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] アミノ酸取り込みによる細胞内代謝シグナルの駆動2019

    • Author(s)
      Shibutani S
    • Organizer
      山口大学研究拠点形成シンポジウム「がんの増殖制御」
    • Related Report
      2018 Research-status Report
  • [Presentation] 細胞内代謝の新規制御メカニズムの発見とがん細胞への応用2019

    • Author(s)
      Shibutani S
    • Organizer
      山口大学研究推進体「小動物のガンに対するトランスレーショナル研究ユニット」第2回シンポジウム「さまざまな視点からガンを斬る」
    • Related Report
      2018 Research-status Report
  • [Presentation] エンドサイトーシスとアミノ酸-タンパク質代謝制御機構の関係2019

    • Author(s)
      Shibutani S
    • Organizer
      第1回HiHA & HIRAKU若手研究者Workshop
    • Related Report
      2018 Research-status Report
    • Invited

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

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