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Elucidating dynamin 2 functions in invadopodia formation by cancer cells and its regulation by Src

Research Project

Project/Area Number 18K07198
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 InstitutionOkayama University

Principal Investigator

Takeda Tetsuya  岡山大学, 医歯薬学総合研究科, 助教 (30302368)

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細胞浸潤 / 浸潤突起 / ポドソーム / ダイナミン / BARドメイン蛋白質 / 浸潤 / BARドメイン
Outline of Final Research Achievements

In this study, we examined functions of dynamin 2 and BAR domain proteins in cell invasion. Dynamin 2 localised to the invadopodia and podosomes playing essential roles in cell invasion. To identify dynamin 2-binding proteins, coimmunoprecipitation-based screening was performed and ten BAR domain proteins were identified. Furthermore, using immunofluorescence microscopy, multiple BAR domain proteins were identified to be localised at the invadopodia and podosomes. Among these BAR domain proteins, PACSIN 2 appeared to regulate cell invasion together with dynamin 2.

Academic Significance and Societal Importance of the Research Achievements

細胞浸潤は,発生や免疫応答,がん転移に関わる細胞運動である.浸潤突起やポドソームは,細胞浸潤を司る膜構造であるが,その形成や制御メカニズムには未解明な点が多い.本研究では,浸潤突起やポドソームの形成に関わるDynamin 2とBARドメイン蛋白質の機能を明らかにした.そのため本研究は,細胞浸潤が関わる発生や免疫応答機構の理解という学術的意義,さらにDynamin 2やBARドメイン蛋白質を分子標的とした新規がん治療法開発への展開などの社会的意義を持つ.

Report

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

    (31 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (2 results) Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (23 results) (of which Invited: 7 results) Remarks (2 results)

  • [Int'l Joint Research] MRC分子生物学研究所(英国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] MRC-LMB(英国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Mutant BIN1-Dynamin 2 complexes dysregulate membrane remodeling in the pathogenesis of centronuclear myopathy2021

    • Author(s)
      Fujise K., Okubo M., Abe T., Yamada H., Nishino I., Noguchi S., Takei K., Takeda T.
    • Journal Title

      Journal of Biological Chemistry

      Volume: 296 Pages: 100077-100077

    • DOI

      10.1074/jbc.ra120.015184

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dynamin 1 is important for microtubule organisation and stabilisation in glomerular podocytes2020

    • Author(s)
      The Mon La , Tachibana, H., Li, S.A., Abe, T., Seiriki, S., Nagaoka, H., Takashima, E., Takeda, T., Ogawa, D., Makino, S., Asanuma, K., Watanabe, M., Tian, X., Ishibe, S., Sakane, A., Sasaki, T., Wada, J., Takei, K., Yamada, H.
    • Journal Title

      FASEB Journal

      Volume: 34 Issue: 12 Pages: 16449-16463

    • DOI

      10.1096/fj.202001240rr

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Phosphorylation of cortactin by cyclin-dependent kinase-5 modulates actin bundling by the dynamin 1-cortactin ring-like complex and formation of filopodia and lamellipodia in NG108-15 glioma-derived cells2019

    • Author(s)
      Abe, T., La, T.M., Miyagaki, Y., Oya, E., Wei, F.Y., Sumida, K., Fujise, K., Takeda, T., Tomizawa, K., Takei, K., Yamada, H.
    • Journal Title

      Int J Oncol.

      Volume: 54(2) Pages: 550-558

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Novel Membrane Fission Mechanism by Dynamin Complex: Clusterase Model2019

    • Author(s)
      竹居 孝二,山田 浩司,竹田 哲也
    • Journal Title

      Seibutsu Butsuri

      Volume: 59 Issue: 5 Pages: 255-261

    • DOI

      10.2142/biophys.59.255

    • NAID

      130007718913

    • ISSN
      0582-4052, 1347-4219
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 再構成アプローチで解明する中心核ミオパチーの発症機序と診断応用への試み2021

    • Author(s)
      竹田 哲也
    • Organizer
      2020(R2)年度 筋ジストロフィー研究班合同班会議
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Dysregulated membrane remodeling in pathogenesis of congenital diseases2020

    • Author(s)
      Fujise, K., Okubo, M., Abe, T., Yamada, H., Nishino, I., Takei, K., Noguchi, S. and Takeda, T.
    • Organizer
      第58回日本生物物理学会年会,シンポジウム「膜のリモデリングと組織化の分子基盤」
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 細胞の形態形成における膜-細胞骨格の動的相互作用2020

    • Author(s)
      竹田 哲也,藤瀬 賢志郎,山田 浩司,竹居 孝二
    • Organizer
      第72回日本細胞生物学会大会,ワークショップ「細胞操作と定量イメージングで知る細胞骨格ダイナミズム」
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 筋疾患変異型BARドメイン蛋白質BIN1による膜リモデリング異常の解析2020

    • Author(s)
      藤瀬賢志郎,山田浩司,竹居孝二,竹田哲也
    • Organizer
      2020年生体運動研究合同班会議
    • Related Report
      2020 Annual Research Report
  • [Presentation] Unveiling functions of Dynamin and BAR domain proteins in podosome2020

    • Author(s)
      Li Jianzhen,Liu Man,岡本瑞生,Kristina Curry,山田浩司,竹居孝二,竹田哲也
    • Organizer
      2020年生体運動研究合同班会議
    • Related Report
      2020 Annual Research Report
  • [Presentation] 再構成アプローチで解明する中心核ミオパチーの発症機序と診断応用への試み2020

    • Author(s)
      竹田 哲也
    • Organizer
      令和2年度「筋レポジトリーの拡充とそれを活用した筋ジストロフィー関連疾患の病態解明と診断・治療法開発」(2-5)西野班会議
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Dysregulated membrane remodeling in pathogenesis of congenital diseases2020

    • Author(s)
      Fujise, K., Okubo, M., Abe, T., Yamada, H., Nishino, I., Takei, K., Noguchi, S. and Takeda, T.
    • Organizer
      第58回日本生物物理学会年会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 細胞の形態形成における膜-細胞骨格の動的相互作用2020

    • Author(s)
      竹田 哲也,藤瀬 賢志郎,山田 浩司,竹居 孝二
    • Organizer
      第72回日本細胞生物学会大会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 筋疾患変異型BARドメイン蛋白質BIN1による膜リモデリング異常の解析2020

    • Author(s)
      藤瀬 賢志郎,山田 浩司,竹居 孝二,竹田 哲也
    • Organizer
      2020年生体運動研究合同班会議
    • Related Report
      2019 Research-status Report
  • [Presentation] Unveiling functions of Dynamin and BAR domain proteins in podosome2020

    • Author(s)
      Li Jianzhen,Liu Man,岡本 瑞生,Kristina Curry,山田 浩司,竹居 孝二,竹田 哲也
    • Organizer
      2020年生体運動研究合同班会議
    • Related Report
      2019 Research-status Report
  • [Presentation] ダイナミン GTPアーゼはアクチン線維の束化と分散を機械的に制御する2019

    • Author(s)
      竹居 孝二, The Mon La, 阿部 匡, 竹田 哲也, 藤原 郁子,成田 哲博
    • Organizer
      第57回日本生物物理学会年会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] ダイナミンのSNP変異が引き起こすミオパチーとニューロパチーの発症メカニズム解析システム2019

    • Author(s)
      佐藤愛美,藤瀬賢志郎,竹田哲也,戸井基道
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Amphiphysin 1 is important for actin cytoskeletal regulation with synaptopodin in glomerular podocytes2019

    • Author(s)
      The Mon La, Tadashi Abe, Masayuki Morita, Eizo Takashima, Tetsuya Takeda, Katsuhiko Asanuma, Kohji Takei, Hiroshi Yamada
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Regulation of skeletal muscle membrane robustness by membrane remodeling proteins BIN1 and Dynamin-22019

    • Author(s)
      Kenshiro Fujise, Hiroshi Yamada, Kohji Takei, Tetsuya Takeda
    • Organizer
      第7回若手による骨格筋細胞研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] Mechanical stress-responsive membrane remodeling in muscle cells2019

    • Author(s)
      藤瀬 賢志郎, 山田 浩司, 竹居 孝二, 竹田 哲也
    • Organizer
      第57回日本生物物理学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 筋細胞膜リモデリングにおけるメカニカルストレス応答の解析2019

    • Author(s)
      藤瀬 賢志郎, 山田 浩司, 竹居 孝二, 竹田 哲也
    • Organizer
      日本筋学会第5回学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 中心核ミオパチー型BIN1およびDNM2変異体による膜リモデリング異常の解析2019

    • Author(s)
      藤瀬 賢志郎, 山田 浩司, 竹居 孝二, 竹田 哲也
    • Organizer
      第71回日本細胞生物学会大会 (日本蛋白質科学会合同大会)
    • Related Report
      2019 Research-status Report
  • [Presentation] 筋細胞膜の形態形成における張力応答メカニズムの解析2019

    • Author(s)
      藤瀬 賢志郎, 山田 浩司, 竹居 孝二, 竹田 哲也
    • Organizer
      2019年生体運動研究合同班会議
    • Related Report
      2018 Research-status Report
  • [Presentation] ダイナミンによる浸潤突起形成に関わる新規因子の探索2019

    • Author(s)
      岡本 瑞生, 李 建振, 山田 浩司, 竹居 孝二, 竹田 哲也
    • Organizer
      2019年生体運動研究合同班会議
    • Related Report
      2018 Research-status Report
  • [Presentation] Elucidating pathogenesis of congenital muscular and neuronal diseases caused by defective membrane remodeling of dynamin GTPase2018

    • Author(s)
      竹田 哲也, 藤瀬 賢志郎, 延永 裕太, 山田 浩司, 竹居 孝二
    • Organizer
      第56回日本生物物理学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 膜リモデリングおよびリン脂質代謝異常に起因する先天性ミオパチー発症機序の解明2018

    • Author(s)
      藤瀬 賢志郎, 背山 佳穂, 山下 恭加, 山田 浩司, 戸井 基道, 竹居 孝二, 竹田 哲也
    • Organizer
      日本筋学会第4回学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Using non-mammalian model organisms for human disease study and drug screening2018

    • Author(s)
      Tetsuya Takeda and Motomichi Doi
    • Organizer
      第70回日本細胞生物学会 第51回日本発生生物学会合同大会 シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] Elucidating pathogenesis of congenital myopathy caused by defective membrane remodeling2018

    • Author(s)
      Kenshiro Fujise, Kaho Seyama, Yasuka Yamashita, Hiroshi Yamada, Kohji Takei and Tetsuya Takeda
    • Organizer
      第70回日本細胞生物学会 第51回日本発生生物学会合同大会
    • Related Report
      2018 Research-status Report
  • [Remarks]

    • URL

      https://researchmap.jp/ttakeda1126

    • Related Report
      2020 Annual Research Report
  • [Remarks] 岡山大学大学院医歯薬学総合研究科生化学分野

    • URL

      http://www.okayama-u.ac.jp/user/biochem/index.html

    • Related Report
      2018 Research-status Report

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

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