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Clarification of the mechanism of oral carcinogenesis by the defect of degradation of chromosome passenger complex protein

Research Project

Project/Area Number 16H05542
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionThe University of Tokushima

Principal Investigator

KUDO Yasusei  徳島大学, 大学院医歯薬学研究部(歯学域), 准教授 (50314753)

Co-Investigator(Kenkyū-buntansha) 岡本 哲治  広島大学, 医歯薬保健学研究科(歯), 教授 (00169153)
宮本 洋二  徳島大学, 大学院医歯薬学研究部(歯学域), 教授 (20200214)
河合 秀彦  広島大学, 医歯薬保健学研究科(薬), 准教授 (30379846)
石丸 直澄  徳島大学, 大学院医歯薬学研究部(歯学域), 教授 (60314879)
常松 貴明  徳島大学, 大学院医歯薬学研究部(医学域), 助教 (70726752)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2018: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Keywords細胞周期 / 染色体パッセンジャー複合体 / ユビキチン分解 / 口腔癌 / 細胞分裂 / 染色体パッセンジャータンパク / Borealin / 発癌
Outline of Final Research Achievements

Accurate distribution of replicated chromosomes in cell division is essential for the development of an individual and the inheritance of life to the next generation. The excess or deficiency of the number of chromosomes caused by chromosomal segregation abnormality is called chromosomal instability and is an important step to cause carcinogenesis, but the cause has not been clarified yet. In this study, we focused on Borealin, a component of the chromosome-passenger complex that plays an essential role in controlling chromosome segregation. We clarified its mechanism of degradation and its mechanism of oral carcinogenesis.

Academic Significance and Societal Importance of the Research Achievements

本研究では,染色体分配という生命を根本で支える極めて重要なイベントの詳細なメカニズムをユビキチン分解に着目して明らかにし、その制御異常による口腔発癌機構を解明することを目的としている。本研究成果は、ユビキチン分解制御の破綻が染色体分配異常を介して癌化を引き起こすという新たな癌化機構を提唱するものと考える。本研究で着目する染色体分配異常は、癌で必須の異常であることから、特異性の高い分子標的治療薬の開発のみならず、口腔癌の新規診断マーカーとしての応用にも繋がり,新たな診断・治療戦略に発展することが期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (20 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (6 results) Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (10 results) (of which Int'l Joint Research: 5 results,  Invited: 3 results)

  • [Int'l Joint Research] New York University(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] University of Edinburg(英国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] ニューヨーク大学医学部・ハワードヒューズ医学研究所(米国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] エジンバラ大学(英国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] New York University(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] University of Edinburgh(英国)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Expression of USP22 and the chromosomal passenger complex is an indicator of malignant progression in oral squamous cell carcinoma2019

    • Author(s)
      Liu Tian、Liu Jing、Chen Qiuyue、Jin Shengjian、Mi Sisi、Shao Wenhua、Kudo Yasusei、Zeng Sien、Qi Guangying
    • Journal Title

      Oncology Letters

      Volume: 17 Pages: 2040-2046

    • DOI

      10.3892/ol.2018.9837

    • NAID

      120007099371

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Predicting cancer outcome: Artificial intelligence vs. pathologists2019

    • Author(s)
      Kudo Yasusei
    • Journal Title

      Oral Diseases

      Volume: 25 Issue: 3 Pages: 643-645

    • DOI

      10.1111/odi.12954

    • NAID

      120006884847

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Invasion-related factors as potential diagnostic and therapeutic targets in oral squamous cell carcinoma.2018

    • Author(s)
      Siriwardena SBSM, Tsunematsu T, Qi G, Ishimaru N, Kudo Y.
    • Journal Title

      Int J Mol Sci

      Volume: 19 Issue: 5 Pages: 1462-1462

    • DOI

      10.3390/ijms19051462

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Aurora Kinase Inhibitors In Head And Neck Cancer.2018

    • Author(s)
      Qi G, Liu J, Mi S, Tsunematsu T, Jin S, Shao W, Liu T, Ishimaru N, Tang B, Kudo Y.
    • Journal Title

      Curr Top Med Chem.

      Volume: - Issue: 3 Pages: 199-213

    • DOI

      10.2174/1568026618666180112163741

    • NAID

      120006729373

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 染色体パッセンジャー複合体による多能性幹細胞の未分化能維持機構2019

    • Author(s)
      常松貴明, 河合秀彦, 石丸直澄, William C. Earnshaw, Michele Pagano, 工藤保誠
    • Organizer
      第36回染色体ワークショップ
    • Related Report
      2018 Annual Research Report
  • [Presentation] 細胞周期調節を標的としたがん幹細胞の分化誘導とその臨床応用の可能性2018

    • Author(s)
      工藤保誠
    • Organizer
      2018先端医学研究交流セミナー「がん・白血病ー先端研究の現状ー」
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] APC/C-Cdh1-mediated degradation of Borealin triggers differentiation of pluripotent stem cells2018

    • Author(s)
      Takaaki Tsunematsu, Naozumi Ishimaru, and Yasusei Kudo
    • Organizer
      FASEB meeting “Ubiquitin and Cellular Regulation
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 多能性幹細胞においてAPC/CCdh1によるBorealinの分解は分化を誘発する.常松貴明2018

    • Author(s)
      常松貴明、石丸直澄、工藤保誠
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Chromosome passenger complex protein, Borealin is regulated by APC/CCdh1 ubiquitin ligase complex2017

    • Author(s)
      Takaaki Tsunematsu, Naozumi Ishimaru, Yasusei Kudo
    • Organizer
      Cold Spring Harbor Laboratory Meeting: The Ubiquitin Family
    • Place of Presentation
      Cold Spring Harbor(米国)
    • Year and Date
      2017-04-18
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Chromosome passenger complex protein, Borealin is regulated by APC/C-Cdh1 ubiquitin ligase complex2017

    • Author(s)
      Tsunematsu T, Ishimaru N, Kudo Y.
    • Organizer
      Cold Spring Harbor Laboratory Meeting, “Ubiquitin family”
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Chromosome passenger complex protein, Borealin is regulated by APC/C-Cdh1 ubiquitin ligase complex2017

    • Author(s)
      Tsunematsu T, Ishimaru N, Kudo Y.
    • Organizer
      Gordon Research Conference “Cell Growth & Proliferation"
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 胎児性癌細胞におけるユビキチンプロテアソーム経路による未分化性維持機構2017

    • Author(s)
      常松 貴明, 工藤 保誠, 山田 安希子, 新垣 理恵子, 小川 博久, 常山 幸一, 石丸 直澄
    • Organizer
      第106回日本病理学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] The APC/CCdh1-Borealin axis has critical role in the maintenance of undifferentiated state in embryonal carcinoma cells.2016

    • Author(s)
      Takaaki Tsunematsu, Naozumi Ishimaru, Yasusei Kudo
    • Organizer
      8th International Conference SUMO, Ubiquitin, UBL Proteins- Implications for Human Diseases
    • Place of Presentation
      上海市(中国)
    • Year and Date
      2016-10-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 基礎系教育講演「細胞周期制御異常とがん」2016

    • Author(s)
      工藤保誠
    • Organizer
      四国歯学会第49回例会
    • Place of Presentation
      徳島大学歯学部(徳島県・徳島市)
    • Related Report
      2016 Annual Research Report
    • Invited

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Published: 2016-04-21   Modified: 2022-06-10  

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