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Analysis of the mechanism of cancer progression that overcome the cellular senescence by activated Ras

Research Project

Project/Area Number 24501327
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor biology
Research Institution防衛大学校(総合教育学群、人文社会科学群、応用科学群、電気情報学群及びシステム工学群) (2013-2014)
National Center of Neurology and Psychiatry (2012)

Principal Investigator

UEKITA TAKAMASA  防衛大学校(総合教育学群、人文社会科学群、応用科学群、電気情報学群及びシステム工, その他部局等, 准教授 (50373402)

Co-Investigator(Renkei-kenkyūsha) YAMAGUCHI Hideki  国立がん研究センター, 難治進行がん研究分野, ユニット長 (10345035)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsRas / CDCP1 / MMP / Invasion / Metastasis / ERK / Autophagy / MT1-MMP
Outline of Final Research Achievements

In normal cells, the expression of activated Ras induces cell death by cellular senescense, but recent evidence indicates a role in cancer progression, including metastasis and invasion; however, the mechanism is still unknown.
In this study, we present in vitro evidence that CDCP1 might play an essential role in supressing autophagy and cancer cell death by cellular scenesense. Activated Ras induces CDCP1 expression through authentic Ras-ERK signaling pathway. Moreover, we found that CDCP1 induced by activated Ras controls cancer cell invasion through regulation of MMPs, such as MT1-MMP, MMP-2 and MMP-9.
These results indicate that CDCP1 is an essencial regulator of the cancer progression that overcome cell senescense.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (17 results)

All 2014 2013 2012

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (13 results)

  • [Journal Article] Flotillin-1 regulates oncogenic signaling in neuroblastoma cells by regulating ALK membrane association.2014

    • Author(s)
      Tomiyama A, Uekita T, Kamata R, Sasaki K, Takita J, Ohira M, Nakagawara A, Kitanaka C, Mori K, Yamaguchi H, Sakai R.
    • Journal Title

      Cancer Res.

      Volume: 74(14) Issue: 14 Pages: 3790-3801

    • DOI

      10.1158/0008-5472.can-14-0241

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oncogenic Ras/ERK signaling activates CDCP1 to promote tumor invasion and metastasis2014

    • Author(s)
      Uekita T, Fujii S et al.
    • Journal Title

      Molecular Cancer Research

      Volume: 12 Issue: 10 Pages: 1449-1459

    • DOI

      10.1158/1541-7786.mcr-13-0587

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Suppression of autophagy by CUB domain-containing protein 1 signaling is essential for anchorage-independent survival of lung cancer cells.2013

    • Author(s)
      Uekita T, Fujii S, Miyazawa Y, Hashiguchi A, Abe H, Sakamoto M, Sakai R.
    • Journal Title

      Cancer Sci.

      Volume: 104 Issue: 7 Pages: 865-870

    • DOI

      10.1111/cas.12154

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] CDCP1 regulates the function of MT1-MMP and invadopodia-mediated invasion of cancer cells.2013

    • Author(s)
      Miyazawa Y, Uekita T, Ito Y, Seiki M, Yamaguchi H, Sakai R.
    • Journal Title

      Mol Cancer Res.

      Volume: 11(6) Issue: 6 Pages: 628-37

    • DOI

      10.1158/1541-7786.mcr-12-0544

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] CDCP1細胞外ドメインは、同種多量体形成によってがん細胞の運動能を促進する。2014

    • Author(s)
      澤山忠司、上北尚正
    • Organizer
      第37回分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Oncogenic Ras-ERK signaling activates CDCP1 pathway to promote tumor invasion and metastasis2014

    • Author(s)
      上北尚正、堺隆一
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Analysis of anchorage-independent growth signaling in small cell lung cancer (SCLC)2014

    • Author(s)
      上北尚正、堺隆一
    • Organizer
      第23回日本がん転移学会学術集会・総会
    • Place of Presentation
      金沢
    • Year and Date
      2014-07-10 – 2014-07-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] 癌細胞の足場非依存性におけるCDCP1シグナルを介したAutophagy抑制の重要性2013

    • Author(s)
      上北尚正
    • Organizer
      第22回日本がん転移学会学術集会・総会
    • Place of Presentation
      長野
    • Related Report
      2013 Research-status Report
  • [Presentation] CDCP1 regulates the function of MT1-MMP and invadopodia-mediated invasion of Cancer cells2013

    • Author(s)
      T Uekita, R Sakai
    • Organizer
      The 7th Mechanisms & Models of Cancer
    • Place of Presentation
      Salk Inst. La Jolla USA
    • Related Report
      2013 Research-status Report
  • [Presentation] CDCP1はMT1-MMPの機能と浸潤突起を介したがん細胞の浸潤を制御する2013

    • Author(s)
      上北尚正、山口英樹、堺隆一
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] 新規ALK結合蛋白質であるFlotillin-1はendocytosisを介してALKシグナルを制御する2013

    • Author(s)
      富山新太、上北尚正、堺隆一
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] Oncogenic Ras-ERK signaling requires activation of CDCP1 pathway for promotion of tumor metastasis2013

    • Author(s)
      Ryuichi Sakai, Takamasa Uekita
    • Organizer
      9th AACR-Japanese Cancer Association Joint Conference
    • Place of Presentation
      Maui, USA
    • Related Report
      2012 Research-status Report
  • [Presentation] ALKのネガティブレギュレータFLOT1の神経芽腫における役割2013

    • Author(s)
      富山新太、上北尚正
    • Organizer
      第19回神経芽腫研究会
    • Place of Presentation
      千葉
    • Related Report
      2012 Research-status Report
  • [Presentation] Ras-ERKシグナルによる癌の転移能の亢進はCDCP1発現誘導を介する2012

    • Author(s)
      上北尚正
    • Organizer
      第71回日本癌学会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] CDCP1はRasにより発現誘導され、癌細胞の足場非依存性及び、浸潤・転移に関与する2012

    • Author(s)
      上北尚正
    • Organizer
      第21回日本がん転移学会
    • Place of Presentation
      広島
    • Related Report
      2012 Research-status Report
  • [Presentation] Flotillin-1 is a novel ALK binding protein which regulates ALK signaling through receptor endocytosis2012

    • Author(s)
      Arata Tomiyama, Takamasa Uekita
    • Organizer
      Advances in Neuroblastoma Research Conference 2012
    • Place of Presentation
      Tront, CA
    • Related Report
      2012 Research-status Report
  • [Presentation] 新規ALK結合蛋白質Flotillin-1はendocytosisを介してALKシグナルを制御する2012

    • Author(s)
      富山新太、上北尚正
    • Organizer
      第71回日本癌学会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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