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Toward understanding the mechanism of the relationship between CD133 and autophagy

Research Project

Project/Area Number 18K07223
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 Institution地方独立行政法人佐賀県医療センター好生館(ライフサイエンス研究所)

Principal Investigator

IZUMI HIDEKI  地方独立行政法人佐賀県医療センター好生館(ライフサイエンス研究所), ライフサイエンス研究所, 部長 (10397987)

Co-Investigator(Kenkyū-buntansha) 李 元元  千葉県がんセンター(研究所), その他部局等, その他 (00392259)
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)
KeywordsCD133 / がん幹細胞 / オートファジー / 中心体 / 非対称分裂
Outline of Final Research Achievements

CD133 is a transmembrane protein and has been recently reported to be localized in cytoplasms. However, the mechanism of action and function of cytoplasmic CD133 remains unknown. In this study, CD133 interacts with HDAC6 and is transported via the dynein-based transport system to the pericentrosome region. Subsequently, endosomal CD133 inhibit the initiation of autophagy, resulting in suppression of cell differentiation such as neurite outgrowth and primary cilia formation. Furthermore, endosome CD133 itself was found to be degraded by p62 / SQSTM1-mediated selective autophagy. Finally, endosomal CD133 cooperated with nuclear beta-catenin to induce asymmetric cell division.

Academic Significance and Societal Importance of the Research Achievements

私たちの研究成果は、中心体近傍型のCD133エンドソームが癌細胞の未分化状態を維持する上で重要な役割を果たすことを示し、また、中心体近傍型のCD133エンドソームは、核のベータ・カテニンと協力して、オートファジー活性に基づく非対称分裂を誘導することを示し、がん幹細胞マーカーの新しい機能を明らかにした。

Report

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

    (13 results)

All 2020 2019 2018 Other

All Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (4 results) (of which Int'l Joint Research: 1 results) Remarks (4 results)

  • [Journal Article] CD133 and centrosomes- How CD133 inhibits autophagy and induces the undifferentiated state of cancer cells at centrosomes2020

    • Author(s)
      Izumi Hideki
    • Journal Title

      Journal of Cancer Biology

      Volume: 1 Issue: 1 Pages: 7-9

    • DOI

      10.46439/cancerbiology.1.002

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Role of MYCN in Symmetric vs. Asymmetric Cell Division of Human Neuroblastoma Cells2020

    • Author(s)
      Izumi Hideki、Kaneko Yasuhiko、Nakagawara Akira
    • Journal Title

      Frontiers in Oncology

      Volume: 10 Pages: 570815-570815

    • DOI

      10.3389/fonc.2020.570815

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] BMP4 induces asymmetric cell division in human glioma stem-like cells2020

    • Author(s)
      Koguchi Motofumi、Nakahara Yukiko、Ito Hiroshi、Wakamiya Tomihiro、Yoshioka Fumitaka、Ogata Atsushi、Inoue Kohei、Masuoka Jun、Izumi Hideki、Abe Tatsuya
    • Journal Title

      Oncology Letters

      Volume: 19 Pages: 1247-1254

    • DOI

      10.3892/ol.2019.11231

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Recycling endosomal CD133 functions as an inhibitor of autophagy at the pericentrosomal region2019

    • Author(s)
      Hideki Izumi, Yuanyuan Li, Masami Shibaki, Daisuke Mori, Michio Yasunami, Seiji Sato, Hisashi Matsunaga, Takao Mae, Kenji Kodama, Takehiko Kamijo, Yasuhiko Kaneko & Akira Nakagawara
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 2236-2236

    • DOI

      10.1038/s41598-019-39229-8

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PPP3CB contributes to poor prognosis through activating nuclear factor of activated T-cells signaling in neuroblastoma2018

    • Author(s)
      Shakhova Irina、Li Yuanyuan、Yu Fan、Kaneko Yoshiki、Nakamura Yohko、Ohira Miki、Izumi Hideki、Mae Takao、Varfolomeeva Svetlana R.、Rumyantsev Alexander G.、Nakagawara Akira
    • Journal Title

      Molecular Carcinogenesis

      Volume: 58 Issue: 3 Pages: 426-435

    • DOI

      10.1002/mc.22939

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 腫瘍不均一性の原動力となるCD133陽性神経芽腫細胞のオートファジーに基づく新たな非対称分裂機構の解明.2020

    • Author(s)
      泉 秀樹、金子安比古、中川原 章
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] BMP4 induces to asymmetric cell division in human glioma stem-like cells2019

    • Author(s)
      Motofumi Koguch, Hideki Izumi, Yukiko Nakahara, Hiroshi Ito, Tomihiro Wakamiya, Fumitaka Yoshioka, Atsushi Ogata, Kohei Inoue, Jun Masuoka, Tatsuya Abe
    • Organizer
      The 24th Annual Scientific Meeting and Education Day of The Society for Neuro- Oncology
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] がん幹細胞マーカーCD133は細胞内に輸送されて中心体近傍に局在し、オートファジ ーを抑制してがん細胞の未分化能を維持する2018

    • Author(s)
      泉 秀樹
    • Organizer
      第37回 分子病理学研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] がん幹細胞マーカーCD133は細胞内に輸送されて中心体近傍に局在し、オートファジ ーを抑制してがん細胞の未分化能を維持する2018

    • Author(s)
      泉 秀樹、李 元元、上條岳彦、金子安比古、中川原 章
    • Organizer
      第77回 日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Remarks] がん細胞の親玉の分化抑えるたんぱく質の機能解明

    • URL

      https://www.asahi.com/articles/ASM2N3W0PM2NTTHB003.html

    • Related Report
      2018 Research-status Report
  • [Remarks] 好生館ライフサイエンス研究所部長 泉秀樹さん /佐賀

    • URL

      https://mainichi.jp/articles/20190224/ddl/k41/070/180000c

    • Related Report
      2018 Research-status Report
  • [Remarks] がん幹細胞の悪性維持 タンパク質の関与解明 好生館研究者ら発表 治療法に期待

    • URL

      https://www.nishinippon.co.jp/nnp/medical/article/492581/

    • Related Report
      2018 Research-status Report
  • [Remarks] がん幹細胞マーカーの機能解明 県医療センター好生館研究所

    • URL

      https://www.saga-s.co.jp/articles/-/339834

    • Related Report
      2018 Research-status Report

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

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