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Analysis of tumorigenesis by autophagy failure and centrosomal dysregulation.

Research Project

Project/Area Number 17K15613
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pathological medical chemistry
Research InstitutionTokyo Medical and Dental University

Principal Investigator

HONDA Shinya  東京医科歯科大学, 難治疾患研究所, 助教 (90532672)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsオートファジー / がん / 中心体
Outline of Final Research Achievements

An abnormal centrosome number causes genomic instability, which leads to tumorigenesis. Recently, we showed that autophagy also regulates the number of centrosomes in a cell, via the degradation of Cep63. Thus, a defect in autophagy causes Cep63 accumulation, which in turn forms multiple centrosome (Nat. Commun., 2016).
In this study, we analyzed whether the failure of centrosome regulation by autophagy is related to tumorigenesis. As a result of carrying out tumorigenesis model mice and xenograft experiments, it has become clear that disruption of the centrosome control mechanism by autophagy contributes to tumorigenesis and tumor malignancy. In addition, analysis of whether a similar increase in the number of centrosomes was also observed in human cancer cell lines showed a significantly increase in certain cancer groups.

Academic Significance and Societal Importance of the Research Achievements

半数を超えるがんが中心体を過剰に有していると考えられる為、がん化の過程における中心体数の制御破綻の解明は発がん抑制や腫瘍の悪性化、増大化を妨げる事ができると考えられる。本研究は、申請者のグループが発見したオートファジーによる中心体数の制御機構が、がんに関与することを明らかにした研究であり、オートファジーによる中心体制御機構の破綻が発がんや腫瘍の悪性化に貢献することを明らかにした。本研究結果からオートファジー不全が腫瘍の悪性化に関与することが明らかになったため、オートファジー活性の惹起によりがん抑制効果が得られると考えられ、創薬の基盤となることが期待される。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (7 results)

All 2019 2018 2017

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (2 results)

  • [Journal Article] Beclin 1 regulates recycling endosome and is required for skin development in mice2019

    • Author(s)
      Noguchi Saori、Honda Shinya、Saitoh Tatsuya、Matsumura Hiroyuki、Nishimura Emi、Akira Shizuo、Shimizu Shigeomi
    • Journal Title

      Communications Biology

      Volume: 2 Issue: 1 Pages: 37-37

    • DOI

      10.1038/s42003-018-0279-0

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prediction of intracellular targets of a small compound by analyzing peptides presented on MHC class I2019

    • Author(s)
      Sugimoto Yuna、Murohashi Michiko、Arakawa Satoko、Honda Shinya、Shimizu Shigeomi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 508 Issue: 2 Pages: 480-486

    • DOI

      10.1016/j.bbrc.2018.11.089

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Monitoring of Atg5-Independent Mitophagy2017

    • Author(s)
      Arakawa Satoko、Honda Shinya、Torii Satoru、Tsujioka Masatsune、Shimizu Shigeomi
    • Journal Title

      Methods Mol Biol.

      Volume: - Pages: 125-132

    • DOI

      10.1007/7651_2017_16

    • ISBN
      9781493977499, 9781493977505
    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Autophagy controls centrosome number.2017

    • Author(s)
      Honda S, Shimizu S
    • Journal Title

      Oncotarget

      Volume: 8 Issue: 9 Pages: 14277-14278

    • DOI

      10.18632/oncotarget.15362

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular mechanisms and physiological roles of Atg5/Atg7-independent alternative autophagy2017

    • Author(s)
      Arakawa S, Honda S, Yamaguchi H, Shimizu S.
    • Journal Title

      Proceedings of the Japan Academy, Series B

      Volume: 93 Issue: 6 Pages: 378-385

    • DOI

      10.2183/pjab.93.023

    • NAID

      130005696809

    • ISSN
      0386-2208, 1349-2896
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] オートファジーは中心体数を制御することで腫瘍形成を抑制する2018

    • Author(s)
      本田真也、清水重臣
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] オートファジーは中心体数を制御することで腫瘍形成を抑制する2017

    • Author(s)
      本田真也・清水重臣
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2020-03-30  

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