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Molecular mechanism of mitotic spindle adaptation to drastic chromosome number changes

Research Project

Project/Area Number 17K15111
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Cell biology
Research InstitutionHokkaido University

Principal Investigator

Uehara Ryota  北海道大学, 先端生命科学研究院, 准教授 (20580020)

Research Collaborator YAGUCHI Kan  
YAMAMOTO Takahiro  
SHIMADA Masaya  
Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Keywords倍数性 / 細胞分裂 / 中心体 / 染色体 / 紡錘体
Outline of Final Research Achievements

Animal somatic cells are usually in the diploid state, containing two copies of genomes. Abnormal changes in ploidy state (ie. drastic changes in chromosome number) are hallmarks of cancer cells, but it remains largely unknown how cells can manage to survive with abnormal chromosome numbers. In this research, I aimed to elucidate the molecular mechanism through which mitotic and cell cycle regulatory systems can adapt to drastic chromosome number changes. Through cell imaging and comprehensive gene expression analyses, we found characteristic changes in mitotic centrosome structure and cyclin D expression upon ploidy changes, which potentially contribute to cellular adaptation to drastic chromosome number changes.

Academic Significance and Societal Importance of the Research Achievements

倍数性変化はガンに特徴的な細胞異常であり、倍数性変化に伴う細胞制御機構の変化を理解することは、倍数性変化に基づくガン細胞の特異的攻撃法の樹立につながると期待される。本研究で得られた知見は、倍数性変化による影響を受ける具体的な細胞プロセスを特定した点に学術的意義があり、これらのプロセスを標的とすることで倍数性異常細胞の選択的な攻撃を行える可能性を示した点に医学的意義がある。

Report

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

    (16 results)

All 2018 2017 Other

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

  • [Int'l Joint Research] Tata Institute of Fundamental Research(インド)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Semmelweis University(ハンガリー)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Tata Institute of Fundamental Research(India)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] Semmelwies University(Hungary)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research]

    • Related Report
      2017 Research-status Report
  • [Journal Article] Tetraploidy-associated centrosome overduplication in mouse early embryos2018

    • Author(s)
      Yaguchi Kan、Yamamoto Takahiro、Matsui Ryo、Shimada Masaya、Shibanuma Atsuko、Kamimura Keiko、Koda Toshiaki、Uehara Ryota
    • Journal Title

      Communicative & Integrative Biology

      Volume: 11 Issue: 4 Pages: e1526605-e1526605

    • DOI

      10.1080/19420889.2018.1526605

    • NAID

      120006533159

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ploidy-dependent change in cyclin D2 expression and sensitization to cdk4/6 inhibition in human somatic haploid cells.2018

    • Author(s)
      Yaguchi K, Yamamoto T, Shimada M, Sugimoto R, Nakamura K, Ayabe T, Uehara R.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 504 Issue: 1 Pages: 231-231

    • DOI

      10.1016/j.bbrc.2018.08.160

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Uncoordinated centrosome cycle underlies the instability of non-diploid somatic cells in mammals2018

    • Author(s)
      Yaguchi Kan、Yamamoto Takahiro、Matsui Ryo、Tsukada Yuki、Shibanuma Atsuko、Kamimura Keiko、Koda Toshiaki、Uehara Ryota
    • Journal Title

      The Journal of Cell Biology

      Volume: 217 Issue: 7 Pages: 2463-2483

    • DOI

      10.1083/jcb.201701151

    • NAID

      120006533144

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Uncoordinated centrosome cycle underlies the instability of non-diploid somatic cells in mammals2018

    • Author(s)
      矢口 完,山本隆博,松井 崚,塚田祐基, 柴沼篤子, 上村佳子, 幸田敏明, 上原亮太
    • Journal Title

      Journal of Cell Biology

      Volume: 印刷中

    • NAID

      120006533144

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dynamics and function of ERM proteins during cytokinesis in human cells2017

    • Author(s)
      Hiruma Shota、Kamasaki Tomoko、Otomo Kohei、Nemoto Tomomi、Uehara Ryota
    • Journal Title

      FEBS Letters

      Volume: 591 Issue: 20 Pages: 3296-3309

    • DOI

      10.1002/1873-3468.12844

    • NAID

      120006533122

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Novel linekbetween ploidy and centrosome duplication2018

    • Author(s)
      Ryota UEHARA
    • Organizer
      Polyploidy in Organ Development, Repair, and Disease, Mount Desert Island Biological Laboratory
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A novel link between ploidy level and centrosome homeostasis in human somatic cells2018

    • Author(s)
      Kan Yaguchi, Takahiro Yamamoto, Ryota Uehara
    • Organizer
      Joint Annual Meeting of JSDB 51st and JSCB 70th, Workshop
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Novel link between ploidy level and centrosome homeostasis in mammalian somatic cells2017

    • Author(s)
      上原亮太
    • Organizer
      Cold Spring Harber Asia Meeting "Cilia and Centrosomes"
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Novel link between ploidy level and centrosome homeostasis in mammalian somatic cells2017

    • Author(s)
      矢口完(研究協力者)
    • Organizer
      第69回日本細胞生物学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Molecular mechanism of the contractile ring-the plasma membrane interaction during cytokinesis in human cells2017

    • Author(s)
      上原亮太
    • Organizer
      第69回日本細胞生物学会大会 シンポジウム
    • Related Report
      2017 Research-status Report
    • Invited
  • [Remarks] ヒト細胞のゲノムセット数が 2 で安定する理由を解明

    • URL

      https://www.hokudai.ac.jp/news/180508_pr2.pdf

    • Related Report
      2018 Annual Research Report

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

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