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Malignant conversion of epithelial cancers through dysregulation of the p63-MYC pathway

Research Project

Project/Area Number 23590375
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathological medical chemistry
Research InstitutionNational Center of Neurology and Psychiatry

Principal Investigator

YUGAWA Takashi  独立行政法人国立がん研究センター, 研究所, 主任研究員 (80311372)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords分子腫瘍学 / 癌 / 悪性化 / 幹細胞性 / 発現制御 / p63 / MYC
Research Abstract

Cancer cells evolve from normal cells through multiple genetic alterations. In particular, identification of a genetic cause behind the acquisition of the metastatic ability is very important for elucidating the nature of cancer.
In this study, I have found the possibility that p63, master regulator of epithelial development and stemness maintenance, acts as both an oncogene and tumor suppressor by increasing the proliferative capacity of cells while constraining metastatic tumor progression in early stages of carcinogenesis. I propose, for the first time, that up-regulation of c-MYC oncogene cancels the proliferative defect induced by p63 loss, thereby triggering malignant conversion in late stages of epithelial cancer development.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (23 results)

All 2014 2013 2012 2011 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 1 results) Presentation (11 results) (of which Invited: 2 results) Remarks (4 results)

  • [Journal Article] ATM regulates Cdt1 stability during the unperturbed S phase to prevent re-replication.2014

    • Author(s)
      Iwahori S, Kohmon D, Kobayashi J, Tani Y, Yugawa T, Komatsu K, Kiyono T, Sugimoto N, Fujita M.
    • Journal Title

      Cell Cycle

      Volume: 13 Issue: 3 Pages: 471-481

    • DOI

      10.4161/cc.27274

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Noncanonical NOTCH signaling limits self-renewal of human epithelial and induced pluripotent stem cells through ROCK activation.2013

    • Author(s)
      Yugawa T, Nishino K, Ohno S, Nakahara T, Fujita M, Goshima N, Umezawa A, Kiyono T
    • Journal Title

      Molecular and Cellular Biology

      Volume: 33(22) Issue: 22 Pages: 4434-4447

    • DOI

      10.1128/mcb.00577-13

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Heterocomplex Formation by Arp4 and β-Actin Involved in Integrity of the Brg1 Chromatin Remodeling Complex2012

    • Author(s)
      Nishimoto, N.
    • Journal Title

      J. Cell Sci.

      Volume: 125 Pages: 3870-3882

    • DOI

      10.1242/jcs.104349

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A critical role of MYC for transformation of human cells by HPV16 E6E7 and oncogenic HRAS2012

    • Author(s)
      Narisawa-Saito, M.
    • Journal Title

      Carcinogenesis

      Volume: 33 Issue: 4 Pages: 910-917

    • DOI

      10.1093/carcin/bgs104

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The E1 protein of human papillomavirus type 16 is dispensable for maintenance replication of the viral genome2012

    • Author(s)
      Egawa, N., et al
    • Journal Title

      J.Virol.

      Volume: 86 Issue: 6 Pages: 3276-3281

    • DOI

      10.1128/jvi.06450-11

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] An in vitro multistep carcinogenesis model for both HPV-positive and -negative human oral squamous cell carcinomas2011

    • Author(s)
      Zushi Y, Narisawa-Saito M, Noguchi K, Yoshimatsu Y, Yugawa T, Egawa N, Fujita M, Urade M, Kiyono T
    • Journal Title

      Am J Cancer Res

      Volume: 1(7) Pages: 869-881

    • URL

      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3196285/

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chromatin remodeler sucrose nonfermenting 2 homolog (SNF2H) is recruited onto DNA replication origins through interaction with Cdc10 protein-dependent transcript 1 (Cdt1) and promotes pre-replication complex formation2011

    • Author(s)
      Nozomi Sugimoto
    • Journal Title

      The Journal of Biological Chemistry

      Volume: 286 Issue: 45 Pages: 39200

    • DOI

      10.1074/jbc.m111.256123

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] An in vitro multistep carcinogenesis model for both HPV-positive and -negative human oral squamous cell carcinomas.2011

    • Author(s)
      Yusuke Zushi
    • Journal Title

      American Journal of Cancer Research

      Volume: 1(7) Pages: 869-881

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Non-canonical NOTCH signaling limits self-renewal of human keratinocytes through ROCK activation.(非古典的NOTCHシグナルはROCKの活性化を介して角化細胞の自己複製能を制限する)2013

    • Author(s)
      温川恭至, 大野真一, 中原知美, 藤田雅俊, 五島直樹, 清野透
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸(示説発表)
    • Year and Date
      2013-12-04
    • Related Report
      2013 Final Research Report
  • [Presentation] Non-canonical NOTCH signaling integrates into ROCK activation to induce differentiation of human keratinocytes.(非古典的NOTCHシグナリングによるROCKの活性化と角化細胞分化)2013

    • Author(s)
      温川恭至, 大野真一, 中原知美, 藤田雅俊, 五島直樹, 清野透
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜(口演)
    • Year and Date
      2013-10-05
    • Related Report
      2013 Final Research Report
  • [Presentation] Molecular mechanisms dictating the biological outcome of p63 loss in human keratinocytes2013

    • Author(s)
      Yugawa T, Kiyono T
    • Organizer
      The 6th International p63/p73 Workshop
    • Place of Presentation
      Kazusa Akademia Park
    • Year and Date
      2013-09-17
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] 非古典的NOTCHシグナルはROCKの活性化を介して角化細胞の自己複製能を制限する2013

    • Author(s)
      温川恭至
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートピアホテル
    • Related Report
      2013 Annual Research Report
  • [Presentation] 非古典的NOTCHシグナリングによるROCKの活性化と角化細胞分化2013

    • Author(s)
      温川恭至
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] Molecular mechanisms dictating the biological outcome of p63 loss in human keratinocytes.2013

    • Author(s)
      Yugawa T
    • Organizer
      The 6th International p63/p73 Workshop
    • Place of Presentation
      Kazusa Akademia Park
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Dysregulation of the p63-MYC pathway in the development of squamous cell carcinomas.(扁平上皮がん発生におけるp63-MYC経路の異常)2012

    • Author(s)
      温川恭至, 藤田雅俊, 清野透
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌(口演)
    • Year and Date
      2012-09-19
    • Related Report
      2013 Final Research Report
  • [Presentation] 扁平上皮がん発生におけるp63-MYC経路の異常2012

    • Author(s)
      温川恭至
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      さっぽろ芸文館
    • Related Report
      2012 Research-status Report
  • [Presentation] -MYC over-expression cancels the proliferative defect triggered by p63 loss in keratinocytes.(c-MYCの過剰発現はp63欠損による角化細胞増殖能の喪失を回避する)2011

    • Author(s)
      温川恭至, 藤田雅俊, 清野透
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋(示設発表)
    • Year and Date
      2011-10-03
    • Related Report
      2013 Final Research Report
  • [Presentation] Regulation of Notch1 gene expression by p53 family members and its disruption by HPV-16 E62011

    • Author(s)
      Yugawa T, Kiyono T
    • Organizer
      ICGEB (International Centre for Genetic Engineering and Biotechnology) DNA Tumour Virus Meeting
    • Place of Presentation
      Trieste, Italy(口演)
    • Year and Date
      2011-07-23
    • Related Report
      2013 Final Research Report
  • [Presentation] c-MYCの過剰発現はp63欠損による角化細胞増殖能の喪失を回避する

    • Author(s)
      温川恭至
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Related Report
      2011 Research-status Report
  • [Remarks]

    • URL

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

    • Related Report
      2013 Final Research Report
  • [Remarks] 独立行政法人国立がん研究センター・研究所・ウイルス発がん研究分野

    • URL

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

    • Related Report
      2013 Annual Research Report
  • [Remarks] 独立行政法人国立がん研究センター 研究所 ウイルス発がん研究分野

    • URL

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

    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

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

    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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