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Elucidation of molecular transport control systems based on cytoskeleton dynamics and new developments in innovative cancer drug discovery.

Research Project

Project/Area Number 19H01064
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
Research InstitutionOkayama University

Principal Investigator

Watanabe Masami  岡山大学, 大学病院, 教授 (70444677)

Co-Investigator(Kenkyū-buntansha) 定平 卓也  岡山大学, 大学病院, 助教 (20733322)
黄 鵬  岡山大学, 中性子医療研究センター, 研究准教授 (00610841)
竹居 孝二  岡山大学, 医歯薬学域, 教授 (40322226)
竹田 哲也  岡山大学, 医歯薬学域, 研究准教授 (30302368)
落合 和彦  日本獣医生命科学大学, 獣医学部, 准教授 (30550488)
野口 洋文  琉球大学, 医学(系)研究科(研究院), 教授 (50378733)
山田 浩司  岡山大学, 医歯薬学域, 研究教授 (80325092)
那須 保友  岡山大学, 医歯薬学域, 教授 (20237572)
Project Period (FY) 2019-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥40,300,000 (Direct Cost: ¥31,000,000、Indirect Cost: ¥9,300,000)
Fiscal Year 2023: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Fiscal Year 2022: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
Fiscal Year 2021: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Fiscal Year 2020: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Fiscal Year 2019: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywords癌創薬 / 細胞内輸送 / in vivo投与 / 細胞骨格 / エンドサイトーシス / in vivo投与法 / 癌 / Dynamin / 間葉系幹細胞 / 幹細胞 / in vivo投与モデル / microtubule / 尿路性器癌
Outline of Research at the Start

前立腺癌を含む各種癌疾患に対する新規治療法の開発は癌治療の分野で喫緊の課題であり、学術的に新しい切り口での癌創薬が求められている。本研究では、前立腺癌の悪性進展とAndrogen不応性のKeyとなるシグナル分子群の細胞内輸送における知見を踏まえ、癌細胞を中心とする各種細胞において、REIC/Dkk-3、SGTA、Tctex-1、Dyneinモーター、Dynaminおよび細胞骨格因子が関わる細胞内分子輸送システムの制御機構を解明する。

Outline of Final Research Achievements

In research using various cancer cells, we have analyzed the function of dynamin and its related molecules in cytoskeleton dynamics, and have obtained results. In research using normal cells, we have also conducted research on the relationship between dynamin and microtubules in glomerular podocytes, and found that dynamin may play a role in the formation of microtubule bundles, thereby stabilizing microtubules. From the perspective of cancer drug discovery, we have established an animal experiment system using dogs to elucidate the mechanism of action of candidate drugs by endoscopic in vivo administration, making it possible to evaluate the efficacy of various drugs using new drug administration techniques.

Academic Significance and Societal Importance of the Research Achievements

前立腺癌の悪性進展とAndrogen不応性のKeyとなるタンパク質分子の細胞内輸送における独自の観点から、微小管輸送ダイナミクスの細胞内分子機構を解明し、新規治療・創薬標的を探索した。また、泌尿器科領域での臨床応用へと結び付けていくための大動物を用いたin vivo投与の研究手法を確立した。一方で本研究は、様々なタンパク質複合体の働きに焦点を当てて新たな知見の獲得を目指すものでもあり、細胞生物学的にも学術的意義が認められる。

Report

(7 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Comments on the Screening Results   Annual Research Report
  • Research Products

    (3 results)

All 2023 2020

All Journal Article (3 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 3 results,  Open Access: 3 results)

  • [Journal Article] Pacsin 2-dependent N-cadherin internalization regulates the migration behaviour of malignant cancer cells2023

    • Author(s)
      Haymar Wint, Jianzhen Li, Tadashi Abe, Hiroshi Yamada, Takumi Higaki, Yasutomo Nasu, Masami Watanabe, Kohji Takei, Tetsuya Takeda
    • Journal Title

      Journal of Cell Science

      Volume: 136(10) Issue: 10

    • DOI

      10.1242/jcs.260827

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Novel extracellular role of REIC/Dkk-3 protein in PD-L1 regulation in cancer cells.2023

    • Author(s)
      Yuma Gohara, Nahoko Tomonobu, Rie Kinoshita, Junichiro Futami, Lena Audebert, Youyi Chen, Ni Luh Gede Yoni Komalasari, Fan Jiang, Chikako Yoshizawa, Hitoshi Murata, Ken-Ichi Yamamoto, Masami Watanabe, Hiromi Kumon, Masakiyo Sakaguchi
    • Journal Title

      Journal of molecular medicine (Berlin, Germany)

      Volume: 101 Issue: 4 Pages: 431-447

    • DOI

      10.1007/s00109-023-02292-w

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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

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Published: 2019-04-18   Modified: 2025-01-30  

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