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Molecular basis for the dual face of NOTCH1 in the development of squamous cell carcinoma

Research Project

Project/Area Number 26460406
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathological medical chemistry
Research InstitutionNational Cancer Center Japan

Principal Investigator

YUGAWA Takashi  国立研究開発法人国立がん研究センター, 研究所, 主任研究員 (80311372)

Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords分子腫瘍学 / 癌 / 悪性化 / 発現制御 / Notch1 / p63 / Myc / p63
Outline of Final Research Achievements

The most powerful force of tumor cells to erode bodies and eventually kill patients is the acquisition of the metastatic ability and malignant phenotypes. To elucidate the molecular mechanisms of malignant conversion is critical for better understanding the nature of cancer.
In this study, I revealed the molecular mechanism explaining the dual nature of NOTCH1 in the development of squamous cell carcinoma. In normal tissue, NOTCH1 has a role in cellular differentiation of stratified epithelia, such as uterine cervix and skin, and functions as a tumor suppressor. In contrast, NOTCH1 convert its role into a driver for increased motility and invasion in malignant tumor cells. This finding provide a scientific evidence to determine the applicable tumors with a molecular targeted therapy against NOTCH1.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (16 results)

All 2018 2017 2016 2015 2014 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 6 results,  Acknowledgement Compliant: 1 results) Presentation (6 results) Remarks (4 results)

  • [Journal Article] Induction of non-apoptotic programmed cell death by oncogenic RAS in human epithelial cells and its suppression by MYC overexpression.2018

    • Author(s)
      Dendo K, Yugawa T, Nakahara T, Ohno SI, Goshima N, Arakawa H, Kiyono T.
    • Journal Title

      Carcinogenesis

      Volume: 39 Issue: 2 Pages: 202-213

    • DOI

      10.1093/carcin/bgx124

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Roles of the PDZ-binding motif of HPV 16 E6 protein in oncogenic transformation of human cervical keratinocytes.2017

    • Author(s)
      Yoshimatsu Y, Nakahara T, Tanaka K, Inagawa Y, Narisawa-Saito M, Yugawa T, Ohno SI, Fujita M, Nakagama H, Kiyono T.
    • Journal Title

      Cancer Science

      Volume: 108(7) Issue: 7 Pages: 1303-1309

    • DOI

      10.1111/cas.13264

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Human Papillomavirus 16 E6 Upregulates APOBEC3B via the TEAD Transcription Factor.2017

    • Author(s)
      Mori S, Takeuchi T, Ishii Y, Yugawa T, Kiyono T, Nishina H, Kukimoto I.
    • Journal Title

      Journal of Virology

      Volume: 91 Issue: 6

    • DOI

      10.1128/jvi.02413-16

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cdt1-binding protein GRWD1 is a novel histone-binding protein that facilitates MCM loading through its influence on chromatin architecture.2015

    • Author(s)
      Sugimoto N, Maehara K, Yoshida K, Yasukouchi S, Osano S, Watanabe S, Aizawa M, Yugawa T, et al.
    • Journal Title

      Nucleic Acids Res.

      Volume: 43 Issue: 12 Pages: 5898-5911

    • DOI

      10.1093/nar/gkv509

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Activation of NF-κB by Human Papillomavirus 16 E1 Limits E1-Dependent Viral Replication through Degradation of E1.2015

    • Author(s)
      Nakahara T, Tanaka K, Ohno S, Egawa N, Yugawa T, Kiyono T.
    • Journal Title

      Journal of Virology

      Volume: 89 Issue: 9 Pages: 5040-5059

    • DOI

      10.1128/jvi.00389-15

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A human cancer xenograft model utilizing normal pancreatic duct epithelial cells conditionally transformed with defined oncogenes.2014

    • Author(s)
      Inagawa Y, Yamada K, Yugawa T, Ohno SI, Hiraoka N, Esaki M, Shibata T, Aoki K, Saya H and Kiyono T
    • Journal Title

      Carcinogenesis

      Volume: 35 Issue: 8 Pages: 1840-1846

    • DOI

      10.1093/carcin/bgu112

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Non-canonical NOTCH signaling drives malignant progression of squamous cell carcinoma.2017

    • Author(s)
      温川恭至, 中原知美, 藤田雅俊, 清野透
    • Organizer
      第40回 日本分子生物学会・生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Dual roles of p63 and NOTCH1 in the development and progression of squamous cell carcinoma.2017

    • Author(s)
      温川恭至, 中原知美, 藤田雅俊, 清野透
    • Organizer
      第76回 日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] The dual role of p63 in the development of squamous cell carcinoma.2016

    • Author(s)
      温川恭至
    • Organizer
      第75回 日本癌学会学術総会
    • 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 Research-status Report
  • [Presentation] Loss of p63 in MYC-overexpressing cells can trigger malignant conversion through the NOTCH-ROCK pathway.2015

    • Author(s)
      温川恭至
    • Organizer
      第74回 日本癌学会学術総会
    • Place of Presentation
      愛知県 名古屋国際会議場
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] Non-canonical NOTCH signaling activates ROCK to control cellular differentiation.2014

    • Author(s)
      温川恭至
    • Organizer
      第37回 日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] The novel NOTCH-ROCK pathway limits self-renewal of human epithelial and iPS cells.2014

    • Author(s)
      温川恭至
    • Organizer
      第73回 日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-09-26
    • Related Report
      2014 Research-status Report
  • [Remarks] 国立研究開発法人 国立がん研究センター 研究所 発がん・予防研究分野

    • URL

      https://www.ncc.go.jp/jp/ri/division/carcinogenesis_and_prevention/viral_carcinogenesis/index.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] 発がん機構研究グループ 発がん・予防研究分野(ウイルス発がん・予防グループ)ホームページ

    • URL

      http://www.nccri.ncc.go.jp/s003/index.html

    • Related Report
      2016 Research-status Report
  • [Remarks] 発がん機構研究グループ 発がん・予防研究分野(ウイルス発がん・予防グループ)ホームページ

    • URL

      http://www.nccri.ncc.go.jp/s003/

    • Related Report
      2015 Research-status Report
  • [Remarks]

    • URL

      http://www.ncc.go.jp/jp/nccri/divisions/10vir/10vir.html

    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2019-03-29  

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