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Elucidation of molecular mechanisms underlying colorectal tumorigenesis driven by Wnt/c-Myc signaling

Research Project

Project/Area Number 16H04692
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Tumor biology
Research InstitutionThe University of Tokyo

Principal Investigator

Kawasaki Yoshihiro  東京大学, 定量生命科学研究所, 客員准教授 (10376642)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2018: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2016: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
KeywordsWnt / c-Myc / lncRNA
Outline of Final Research Achievements

We identified a direct target of c-Myc, termed MYU, and showed that MYU was upregulated in most colon cancers and required for the tumorigenicity of colon cancer cells. Furthermore, we demonstrated that MYU associated with the RNA binding protein hnRNP-K to stabilize CDK6 expression and thereby promoted the G1-S transition of the cell cycle. These results suggest that the MYU/hnRNP-K/CDK6 pathway functions downstream of Wnt/c-Myc signaling and plays a critical role in the proliferation and tumorigenicity of colon cancer cells.

Academic Significance and Societal Importance of the Research Achievements

転写因子であるc-Mycは様々なシグナル経路のハブ因子として機能することが知られています。そのため、c-Mycを直接阻害する薬剤は大きな副作用があると予想されます。したがって、c-Mycが誘発するがんに対してはMYU、hnRNP-K、CDK6による情報伝達の仕組みががんの分子標的薬を創製する上で重要な標的に成り得ると期待できました。

Report

(4 results)
  • 2019 Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (16 results)

All 2019 2018 2017 2016

All Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 4 results,  Acknowledgement Compliant: 4 results) Presentation (5 results) (of which Invited: 1 results) Book (3 results)

  • [Journal Article] The novel lncRNA CALIC upregulates AXL to promote colon cancer metastasis2019

    • Author(s)
      Kawasaki Y、Miyamoto M、Oda T、Matsumura K、Negishi L、Nakato R、Suda S、Yokota N、Shirahige K、Akiyama T.
    • Journal Title

      EMBO reports

      Volume: 20 Issue: 8

    • DOI

      10.15252/embr.201847052

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sp5 negatively regulates the proliferation of HCT116 cells by upregulating the transcription of p272018

    • Author(s)
      Miyamoto M, Hayashi T, Kawasaki Y, Akiyama T.
    • Journal Title

      Oncol Lett.

      Volume: 15 Pages: 4005-4009

    • DOI

      10.3892/ol.2018.7793

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Novel G-quadruplex-Containing Long non-coding RNA GSEC Antagonizes DHX36 and Modulates Colon Cancer Cell Migration2017

    • Author(s)
      Matsumura K, Kawasaki Y, Miyamoto M, Kamoshida Y, Nakamura J, Negishi L, Suda S, Akiyama T
    • Journal Title

      Oncogene

      Volume: 36 Issue: 9 Pages: 1191-1199

    • DOI

      10.1038/onc.2016.282

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] SP5 negatively regulates the proliferation of HCT116 cells by upregulating the transcription of p272017

    • Author(s)
      Miyamoto M, Hayashi T, Kawasaki Y, Akiyama T
    • Journal Title

      Oncol. Lett.

      Volume: 印刷中

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Long noncoding RNA UPAT promotes colon tumorigenesis by inhibiting degradation of UHRF1.2016

    • Author(s)
      Taniue K, Kurimoto A, Sugimasa H, Nasu E, Takeda Y, Iwasaki K, Nagashima T, Okada-Hatakeyama M, Oyama M, Kozuka-Hata H, Hiyoshi M, Kitayama J, Negishi L, Kawasaki Y, Akiyama T.
    • Journal Title

      Proceedings of the National Academy of Sciences U S A.

      Volume: 113 Issue: 5 Pages: 1273-8

    • DOI

      10.1073/pnas.1500992113

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Genomic Landscape of Esophageal Squamous Cell Carcinoma in a Japanese Population.2016

    • Author(s)
      G. Sawada (他43名, 山本21番目)
    • Journal Title

      Gastroenterology

      Volume: 150 Issue: 5 Pages: 1171-1182

    • DOI

      10.1053/j.gastro.2016.01.035

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Temporal Profiling of Astrocyte Precursors Reveals Parallel Roles for Asef during Development and after Injury2016

    • Author(s)
      Chaboub LS, Manalo JM, Lee HK, Glasgow SM, Chen F, Kawasaki Y, Akiyama T, Kuo CT, Creighton CJ, Mohila CA, Deneen B
    • Journal Title

      J. Neurosci.

      Volume: 36 Pages: 11904-11917

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] MYU, a Target lncRNA for Wnt/c-Myc Signaling, Mediates Induction of CDK6 to Promote Cell Cycle Progression.2016

    • Author(s)
      Kawasaki Y, Komiya M, Matsumura K, Negishi L, Suda S, Okuno M, Yokota N, Osada T, Nagashima T, Hiyoshi M, Okada-Hatakeyama M, Kitayama J, Shirahige K, Akiyama T.
    • Journal Title

      Cell Rep.

      Volume: 16(10) Issue: 10 Pages: 2554-64

    • DOI

      10.1016/j.celrep.2016.08.015

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] The novel lncRNA CALIC upregulates AXL to promote colon cancer metastasis2019

    • Author(s)
      Yoshihiro Kawasaki, Masaya Miyamoto, Kosuke Matsumura, Lumi Negishi, Takeaki Oda, Ryuichiro Nakato2, Sakiko Suda, Naoko Yokota, Katsuhiko Shirahige, Tetsu Akiyama
    • Organizer
      第71回細胞生物学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] The novel lncRNA CALIC upregulates AXL to promote colon cancer metastasis2019

    • Author(s)
      Yoshihiro Kawasaki, Masaya Miyamoto, Kosuke Matsumura, Lumi Negishi, Takeaki Oda, Ryuichiro Nakato2, Sakiko Suda, Naoko Yokota, Katsuhiko Shirahige, Tetsu Akiyama
    • Organizer
      第78回日本癌学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] The novel lncRNA CASCA induces the expression of AXL to promote colon cancer cell migration and drug resistance2017

    • Author(s)
      Yoshihiro Kawasaki, Masaya Miyamoto, Sakiko Suda and Tetsu Akiyama
    • Organizer
      日本癌学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Wnt/c-Myc経路の新規標的lncRNA:MYUはCDK6の発現を誘導して細胞周期を進める2016

    • Author(s)
      川崎 善博、小宮 美文、松村 厚佑、根岸 瑠美、須田 咲希子、奥野 ます美、横田 直子、長田 知也、長嶋 剛史、 日吉 雅也、岡田 眞里子、北山 丈二、白髭 克彦、秋山 徹
    • Organizer
      第39回日本分子生物学会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] The Novel G-quadruplex-Containing lncRNA GSEC Modulates Colon Cancer Cell Migration2016

    • Author(s)
      Kawasaki Y, Akiyama T
    • Organizer
      第75回日本癌学会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Book] サイクリン依存性キナーゼ関連阻害剤, COX, 酸化ストレス, NO関連阻害剤", 阻害剤・活性化剤ハンドブック2019

    • Author(s)
      川崎善博
    • Total Pages
      26
    • Publisher
      羊土社
    • Related Report
      2018 Annual Research Report
  • [Book] 別冊「医学のあゆみ」がん微小環境の病態理解と制御2017

    • Author(s)
      川崎善博, 秋山徹
    • Total Pages
      4
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2017 Annual Research Report
  • [Book] 医学のあゆみ2016

    • Author(s)
      川崎善博, 秋山徹
    • Total Pages
      4
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2021-02-19  

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