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Basic research on cancer therapy development targeting anchorage independence

Research Project

Project/Area Number 15K06850
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)

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学群), 応用科学群, 准教授 (50373402)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords癌転移 / 足場非依存性 / シグナル伝達 / 複合体形成 / 低分子化合物 / CDCP1 / Src / PKCδ / がん転移 / 細胞運動能 / 浸潤 / 細胞内シグナル / 細胞死
Outline of Final Research Achievements

In order to target anchorage-independence, which is a majour function of cancer metastasis, as a target of cancer therapy, we aimed to clarify the control mechanism of anchorage-independence by CUB domain-containing protein 1 ( CDCP1). In this study, we revealed that the extracellular CUB2 domain of CDCP1 is involved in the CDCP1 homoohilic complex formation on the cell membrane and is also important for regulating CDCP1 signal via activation of Src family kinase. In addition, we identified two small-molecular compounds effective for suppressing anchorage-independence by blocking CDCP1 signal and succeeded in suppressing metastasis of gastric cancer cells by mouse peritoneal dissemination model.
These results suggest that CDCP1 is useful candidate for cancer therapy targeting anchorage-independence of cancer cells.

Report

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

    (16 results)

All 2018 2017 2016 2015

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (11 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] The extracellular CUB domain of CDCP1 is involved in cell-cell contact and regulates collective cell migration in BxPC3 cells.2018

    • Author(s)
      Sawayama T, Uekita T
    • Journal Title

      Memoir NDA

      Volume: 印刷中

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Sensitive Microbead-Based Organic Media-Assisted Method for Proteomics Sample Preparation from Dilute and Denaturing Solutions2017

    • Author(s)
      Taoka Masato、Fujii Michihiko、Tsuchiya Masahiro、Uekita Takamasa、Ichimura Tohru
    • Journal Title

      ACS Applied Materials & Interfaces

      Volume: 9 Issue: 49 Pages: 42661-42667

    • DOI

      10.1021/acsami.7b16095

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel small molecule inhibiting CDCP1-PKCδ pathway reduces tumor metastasis and proliferation.2017

    • Author(s)
      Nakashima K, Uekita T, Yano S, Kikuchi JI, Nakanishi R, Sakamoto N, Fukumoto K, Nomoto A, Kawamoto K, Shibahara T, Yamaguchi H, Sakai R.
    • Journal Title

      Cancer Sci.

      Volume: 印刷中 Issue: 5 Pages: 1049-1057

    • DOI

      10.1111/cas.13218

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] TRIM32-Cytoplasmic-Body Formation Is an ATP-Consuming Process Stimulated by HSP70 in Cells.2017

    • Author(s)
      Kawaguchi Y, Taoka M, Takekiyo T, Uekita T, Shoji I, Hachiya N, Ichimura T.
    • Journal Title

      PLoS One

      Volume: 12(1) Issue: 1 Pages: 1-5

    • DOI

      10.1371/journal.pone.0169436

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Augmentation of invadopodia formation in temozolomide-resistant or adopted glioma is regulated by c-Jun terminal kinase-paxillin axis2015

    • Author(s)
      Ueno H, Tomiyama A, Yamaguchi H, Uekita T et al.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 468 Issue: 1-2 Pages: 240-247

    • DOI

      10.1016/j.bbrc.2015.10.122

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] Analysis of FAK-mediated anchorage-independent cell growth in small cell lung cancer.2017

    • Author(s)
      上北尚正
    • Organizer
      第26回がん転移学会学術集会・総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Cleavage of CDCP1 regulates signaling of anchorage-independence through its homophilic complex formation.2017

    • Author(s)
      澤山忠司、上北尚正
    • Organizer
      第26回がん転移学会学術集会・総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] CDCP1細胞外ドメイン依存的な同種多量体形成を介した足場非依存性能の制御機構の解明2017

    • Author(s)
      澤山忠司、上北尚正
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] The possibility of CUB2 domain of CDCP1 extracellular domain as a novel therapeutic target for cancer metastasis.2017

    • Author(s)
      澤山忠司、上北尚正
    • Organizer
      CinBio 2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] Homophilic complex formation of CDCP1 by CUB2 domain regulates lung cancer invasion.2017

    • Author(s)
      Sawayama T, Uekita T
    • Organizer
      NCRI Cancer Conference 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] CDCP1細胞外ドメインによる同種多量体形成はSrcを活性化し肺がん転移を亢進する2016

    • Author(s)
      澤山忠司、上北尚正
    • Organizer
      第39回分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] Dimerization of CDCP1 via extracellular domain regulates anchorage independence by activating Src signaling2016

    • Author(s)
      澤山忠司、上北尚正
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] CDCP1細胞外ドメインによる同種2量体形成はSrcを活性化し癌の足場非依存性を制御する2016

    • Author(s)
      澤山忠司、上北尚正
    • Organizer
      第25回日本がん転移学会学術集会・総会
    • Place of Presentation
      米子コンベンションセンター
    • Year and Date
      2016-07-21
    • Related Report
      2016 Research-status Report
  • [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。2015

    • Author(s)
      澤山忠司、上北尚正
    • Organizer
      BMB2015
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] CDCP1は細胞外ドメインによる同種複合体形成を介してがん細胞の運動能を制御する2015

    • Author(s)
      澤山忠司、上北尚正
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] CDCP1細胞外ドメインは,同種2量体形成によってがん細胞の運動能を制御する。2015

    • Author(s)
      澤山忠司、上北尚正
    • Organizer
      第24回日本がん転移学会学術集会/総会
    • Place of Presentation
      シティプラザ大阪
    • Year and Date
      2015-07-23
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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