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The role of dynamin in actin dynamics: Development of anticancer drugs inhibiting dynamin function

Research Project

Project/Area Number 22501013
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Tumor biology
Research InstitutionOkayama University

Principal Investigator

ABE Tadashi  岡山大学, 医学部, 技術専門職員 (60423282)

Co-Investigator(Kenkyū-buntansha) YAMADA Hiroshi  岡山大学, 大学院・医歯薬学総合研究科, 准教授 (80325092)
WATANABE Masami  岡山大学, 岡山大学病院, 准教授 (70444677)
Co-Investigator(Renkei-kenkyūsha) ASAI Akira  静岡県立大学, 大学院・創薬探索センター, 教授 (60381737)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsダイナミン / がん / 浸潤 / 遊走 / dynasore / アクチン
Research Abstract

In search of more effective inhibitor for dynamin than dynasore, one hundred eighty one dynasore analogues were screened by in vitro actin polymerization assay. N'-(4-(diethylamino)benzylidene)-4-methoxybenzohydrazide (DBHA) was identified as a potent dynamin inhibitor. DBHA strongly inhibited the serum-stimulated ruffle formation, cell migration and invasion. Under these conditions, DBHA showed little toxicity for cultured cancer cell line. Furthermore, we clarified the function of dynamin/cortactin complex in the regulation of actin dynamics. The dynamin/cortactin complexes bundled several actin filaments and the bundling stabilized actin filaments. The actin bundling by dynamin/cortactin complex was necessary for formation of growth cone filopodia and cell migration. These findings might be crucial for developping anti cancer drugs.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (24 results)

All 2013 2012 2011 2010 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (14 results) Book (1 results) Remarks (2 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] Stabilization of actin bundles by a Dynamin 12013

    • Author(s)
      Yamada H, Abe T
    • Journal Title

      Cortactin ring complex is necessary for growth cone filopodia.

      Volume: 33 Issue: 10 Pages: 4514-4526

    • DOI

      10.1523/jneurosci.2762-12.2013

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel gene expression system for detecting viable bladder cancer cells2012

    • Author(s)
      Hideo Ueki, et al
    • Journal Title

      International journal of oncology

      Volume: 41 Pages: 135-140

    • DOI

      10.3892/ijo.2012.1417

    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] REIC/Dkk-3-encoding adenoviral vector as a potentially effective therapeutic agent for bladder cancer.2012

    • Author(s)
      Hirata et al.
    • Journal Title

      Int J Oncol.

      Volume: 41 Issue: 2 Pages: 559-564

    • DOI

      10.3892/ijo.2012.1503

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Use of liposomes to study vesicular transport.2010

    • Author(s)
      竹居孝二
    • Journal Title

      Methods in Molecular Biology

      Volume: 606 Pages: 531-542

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Cortactin ring complex is a mechanochemical device stabilizing actin bundles2012

    • Author(s)
      竹居 孝二、Dynamin GTPase
    • Organizer
      日本生体エネルギー研究会 第38回討論会
    • Place of Presentation
      岡山大学薬学部 (岡山)
    • Year and Date
      2012-12-23
    • Related Report
      2012 Final Research Report
  • [Presentation] Dynamin を標的にした抗遊走、浸潤薬の開発2012

    • Author(s)
      岡崎 奈奈
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡(福岡)
    • Year and Date
      2012-12-16
    • Related Report
      2012 Final Research Report
  • [Presentation] Phosphorylation of cortactin by PKC is a key factor for filopodia formation of growth cone2012

    • Author(s)
      山田 浩司
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡(福岡)
    • Year and Date
      2012-12-15
    • Related Report
      2012 Final Research Report
  • [Presentation] PKC phosphorylation of cortactin is implicated in the regulationof acyin dynamics2011

    • Author(s)
      竹居 孝二
    • Organizer
      第51回米国細胞生物学会大会
    • Place of Presentation
      デンバー(米国)
    • Year and Date
      2011-12-04
    • Related Report
      2012 Final Research Report
  • [Presentation] PKC phosphorylation of cortactin is implicated in the regulation of actin dynamics2011

    • Author(s)
      竹居孝二
    • Organizer
      第51回米国細胞生物学会大会
    • Place of Presentation
      デンバー:米国
    • Year and Date
      2011-12-04
    • Related Report
      2011 Annual Research Report
  • [Presentation] 成長円錐糸状仮足形成におけるCortactinのPKCαによるリン酸化とアクチン制御の可能性2011

    • Author(s)
      山田 浩司
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2011-09-22
    • Related Report
      2012 Final Research Report 2011 Annual Research Report
  • [Presentation] Actin bundle formation by dynamin-cortactin complexes is important for filopodium stability of growth cones2011

    • Author(s)
      山田 浩司
    • Organizer
      日本薬学会第131年会
    • Year and Date
      2011-03-30
    • Related Report
      2012 Final Research Report
  • [Presentation] Actin bundle formation by dynamin-cortactin complexes is important for filopodium stability of growth cones.2011

    • Author(s)
      山田浩司
    • Organizer
      日本薬学会
    • Place of Presentation
      静岡
    • Year and Date
      2011-03-30
    • Related Report
      2010 Annual Research Report
  • [Presentation] Cortactin complex mechanically bundles actin filaments and supports the formation of filopodia.2010

    • Author(s)
      竹居 孝二、Dynamin 1
    • Organizer
      第33回日本神経科学、第53回日本神経化学、第20回日本神経回路学会合同年会
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2010-09-03
    • Related Report
      2012 Final Research Report
  • [Presentation] Dynamin 1/Cortactin complex mechanically bundles actin filaments and supports the formation of filopodia.2010

    • Author(s)
      竹居孝二
    • Organizer
      第33回日本神経科学、第53回日本神経化学、第20回日本神経回路学会合同年会
    • Place of Presentation
      神戸
    • Year and Date
      2010-09-03
    • Related Report
      2010 Annual Research Report
  • [Presentation] Amphiphysin 1 とN-WASPの動的な相互作用はアクチン重合を制御する2010

    • Author(s)
      山田 浩司
    • Organizer
      第33回日本神経科学、第53回日本神経化学、第20回日本神経回路学会合同年会
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2010-09-02
    • Related Report
      2012 Final Research Report
  • [Presentation] Phosphorylation of cortactin by PKC is a key factor for filopodia formation of growth cone

    • Author(s)
      山田 浩司
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡(福岡)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Dynaminを標的にした抗遊走、浸潤薬の開発

    • Author(s)
      岡﨑 奈奈
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡(福岡)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Dynamin GTPase / Cortactin ring complex is a mechanochemical device stabilizing actin bundles

    • Author(s)
      竹居 孝二
    • Organizer
      日本生体エネルギー研究会 第38回討論会
    • Place of Presentation
      岡山大学薬学部 (岡山)
    • Related Report
      2012 Annual Research Report
  • [Book] Use of liposomes to study vesicular transport., Methods in Molecular Biology, 6062010

    • Author(s)
      Takei K, Yamada H, Abe T.
    • Related Report
      2012 Final Research Report
  • [Remarks] (1)「神経伸長制御の仕組みを解明」 山陽新聞、平成25年3月30日

    • Related Report
      2012 Final Research Report
  • [Remarks] (2)「神経細胞をつなげる2種のたんぱく質」読売新聞、平成25年4月8日

    • Related Report
      2012 Final Research Report
  • [Patent(Industrial Property Rights)] フルボキサミンを配合することを特徴とする分子標的型抗癌剤(特に抗脳腫瘍治療薬剤:第二医薬品用途)2012

    • Inventor(s)
      道上宏之、林圭一郎、松井秀樹、山田浩司、竹居孝二、宮地弘幸、浅井章良
    • Industrial Property Rights Holder
      道上宏之、林圭一郎、松井秀樹、山田浩司、竹居孝二、宮地弘幸、浅井章良
    • Industrial Property Number
      2012-263317
    • Filing Date
      2012-11-30
    • Related Report
      2012 Final Research Report
  • [Patent(Industrial Property Rights)] 抗浸潤薬の新規スクリーニング法および抗浸潤剤2012

    • Inventor(s)
      山田浩司、竹居孝二、道上宏之、松井秀樹、浅井章良
    • Industrial Property Rights Holder
      山田浩司、竹居孝二、道上宏之、松井秀樹、浅井章良
    • Industrial Property Number
      2012-137489
    • Filing Date
      2012-06-19
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Patent(Industrial Property Rights)] フルボキサミンを配合することを特徴とする分子標的型抗癌剤(特に抗脳腫瘍治療薬剤:第二医薬品用途)2012

    • Inventor(s)
      道上宏之 他6名
    • Industrial Property Rights Holder
      道上宏之 他6名
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2012-263317
    • Filing Date
      2012-11-30
    • Related Report
      2012 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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