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A study on the mechanism regulating cell motility upon metabolic alterations by PFK1 inhibition

Research Project

Project/Area Number 19K16728
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 50010:Tumor biology-related
Research InstitutionTokyo University of Pharmacy and Life Science (2020)
Institute of Physical and Chemical Research (2019)

Principal Investigator

Kobayashi Hiroki  東京薬科大学, 生命科学部, 助教 (30528683)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsがん代謝 / 解糖系 / 細胞遊走 / PFK1
Outline of Research at the Start

がん細胞は正常細胞とは異なる特殊な代謝機構をもっており、その理解ががん治療法開発につながる。細胞内エネルギー産生に重要な解糖系律速酵素ホスホフルクトキナーゼの活性抑制による解糖系代謝フローの切替はペントースリン酸経路の亢進、それによる酸化ストレス耐性の向上によりがんの悪性化に寄与することが知られるが、申請者はその代謝切替が、がん転移に関与する細胞運動性をも亢進させることを見出した。そこで本研究では解糖系代謝フロー切替によるがん細胞の悪性形質獲得機序の解明を目的とし、「複雑・多様ながん代謝がどのようにがんの悪性化に寄与するか」「がんの弱点は何か」の理解を目指す。

Outline of Final Research Achievements

Understanding of cancer metabolism can lead to the development of new anti-cancer therapies. We have found that the alteration of energy metabolism by PFK1 inhibition in cancer cells enhances cell motility, which is involved in cancer metastasis. In this study, we tried to elucidate mechanisms underlying this phenomenon. We performed metabolic analyses, gene expression analyses, and phonotypic analyses using pharmacological and genetic approaches. Consequently, we succeeded in identifying the responsible gene that enhances the motility of cancer cells upon alteration of energy metabolism.

Academic Significance and Societal Importance of the Research Achievements

エネルギー代謝ががん細胞の悪性化にどのように関わるか、その一端を解明することができた。この成果はがんの治療戦略構築の一助となり、将来的に人類の健康に貢献しうる。

Report

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

    (9 results)

All 2021 2020 2019 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (7 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Remarks (1 results)

  • [Journal Article] Chemical reversal of abnormalities in cells carrying mitochondrial DNA mutations.2021

    • Author(s)
      Kobayashi H, Hatakeyama H, Nishimura H, Yokota M, Suzuki S, Tomabechi Y, Shirouzu M, Osada H, Mimaki M, Goto YI, Yoshida M.
    • Journal Title

      Nat Chem Biol

      Volume: 17 Issue: 3 Pages: 335-343

    • DOI

      10.1038/s41589-020-00676-4

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] 機能低下したミトコンドリアを活性化させる化合物の発見とその応用2021

    • Author(s)
      小林大貴、畠山英之、西村はる菜、横田睦美、鈴木禎史、苫米地由里、白水美香子、長田裕之、三牧正和、後藤雄一、吉田稔
    • Organizer
      日本ミトコンドリア学会主催 J-mit 特別オンラインシンポジウム
    • Related Report
      2020 Annual Research Report
  • [Presentation] 機能低下したミトコンドリアを活性化させる化合物の発見2020

    • Author(s)
      小林大貴、畠山英之、西村はる菜、横田睦美、鈴木禎史、苫米地由里、白水美香子、長田裕之、三牧正和、後藤雄一、吉田稔
    • Organizer
      第43回分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Identification of a novel compound that alters energy metabolism2019

    • Author(s)
      Hiroki Kobayashi, Hiroyuki Osada, and Minoru Yoshida
    • Organizer
      Chemical Biology and Drug Discovery, Cold Spring Harbor Asia
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] A novel compound that alters energy metabolism2019

    • Author(s)
      Hiroki Kobayashi, Hiroyuki Osada, and Minoru Yoshida
    • Organizer
      The Joint Symposium of "10th Korea-Japan Chemical Biology Symposium" and "30th Meeting for New Drug Discovery"
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 解糖系酵素PFK1の合成致死遺伝子同定2019

    • Author(s)
      小林大貴、高瀬翔平、松本健、吉田稔
    • Organizer
      日本ケミカルバイオロジー学会 第14回年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Discovery of a small-molecule compound that modulates the Warburg Effect2019

    • Author(s)
      小林大貴、長田裕之、吉田稔
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 解糖系酵素PFK1の合成致死遺伝子の探索2019

    • Author(s)
      小林大貴、高瀬翔平、吉田稔
    • Organizer
      第23回日本がん分子標的治療学会学術集会
    • Related Report
      2019 Research-status Report
  • [Remarks] プレスリリース

    • URL

      https://www.riken.jp/press/2020/20201110_1/index.html

    • Related Report
      2020 Annual Research Report

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Published: 2019-04-18   Modified: 2022-01-27  

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