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Functional analysis of Lgr5 in colon and ovary cancer

Research Project

Project/Area Number 25290043
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Tumor biology
Research InstitutionThe University of Tokyo

Principal Investigator

Kawasaki Yoshihiro  東京大学, 分子細胞生物学研究所, 准教授 (10376642)

Co-Investigator(Kenkyū-buntansha) OKAMOTO Aikou  東京慈恵会医科大学, 医学部, 教授 (20204026)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2015: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
KeywordsLgr5
Outline of Final Research Achievements

Lgr5 is specifically expressed in stem cells of the intestine and has an essential role in maintaining tissue homeostasis. However, the function of Lgr5 in colorectal tumourigenesis is unclear. We showed that Lgr5 is required for the tumourigenicity of colorectal cancer cells. We also showed that the transcription factor GATA6 directly enhances the expression of Lgr5. Furthermore, we demonstrated that GATA6 is upregulated in colorectal cancer cells due to the downregulation of miR-363, which directly targets GATA6. We found that Reg4, a member of the regenerating islet-derived (REG) family, is also a target of GATA6 and GATA6-mediated activation of Reg4 enhances the tumorigenicity of colon cancer cells. These results suggest that the miR-363-GATA6-LGR5/Reg4 pathway is critical for colorectal tumorigenesis.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (22 results)

All 2016 2015 2014 2013

All Journal Article (12 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 12 results,  Open Access: 4 results,  Acknowledgement Compliant: 4 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results) Book (2 results)

  • [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
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] SP5 negatively regulates the proliferation of HCT116 cells by upregulating the transcription of p27.2016

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

      Oncol. Lett.

      Volume: in press

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] REG4 is a transcriptional target of GATA6 and is essential for colorectal tumorigenesis.2015

    • Author(s)
      Kawasaki Y, Matsumura K, Miyamoto M, Tsuji S, Okuno M, Suda S, Hiyoshi M, Kitayama J, Akiyama T.
    • Journal Title

      Sci. Rep.

      Volume: 5 Issue: 1 Pages: 14291-14291

    • DOI

      10.1038/srep14291

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] SOX9-mediated upregulation of LGR5 is important for glioblastoma tumorigenicity.2015

    • Author(s)
      Hiraoka K, Hayashi T, Kaneko R, Nasu-Nishimura Y, Koyama-Nasu R, Kawasaki Y, Akiyama T.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 460 Issue: 2 Pages: 4097-4109

    • DOI

      10.1016/j.bbrc.2015.03.012

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heterogeneous nuclear ribonucleoprotein K upregulates the kinetochore complex component NUF2 and promotes the tumorigenicity of colon cancer cells2015

    • Author(s)
      Hironobu Sugimasa, Kenzui Taniue, Akiko Kurimoto, Yasuko Takeda, Yoshihiro Kawasaki, Tetsu Akiyama
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: Volume 459, Issue 1 Issue: 1 Pages: 29-35

    • DOI

      10.1016/j.bbrc.2015.02.043

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Asef mediates HGF protective effects against LPS-induced lung injury and endothelial barrier dysfunction.2015

    • Author(s)
      Meng F, Meliton A, Moldobaeva N, Mutlu G, Kawasaki Y, Akiyama T, Birukova AA.
    • Journal Title

      Am J Physiol Lung Cell Mol Physiol

      Volume: 308 Issue: 5 Pages: 452-463

    • DOI

      10.1152/ajplung.00170.2014

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Asef controls vascular endothelial permeability and barrier recovery in the lung.2015

    • Author(s)
      Tian X, Tian Y, Gawlak G, Meng F, Kawasaki Y, Akiyama T, Birukova AA.
    • Journal Title

      Mol Biol Cell.

      Volume: 26 Issue: 4 Pages: 636-650

    • DOI

      10.1091/mbc.e14-02-0725

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] HGF-induced Asef-IQGAP1 Complex Controls Cytoskeletal Remodeling and Endothelial Barrier.2015

    • Author(s)
      Tian Y, Gawlak G, Shah AS, Higginbotham K, Tian X, Kawasaki Y, Akiyama T, Sacks DB, Birukova AA.
    • Journal Title

      J Biol Chem.

      Volume: 290 Issue: 7 Pages: 4097-4109

    • DOI

      10.1074/jbc.m114.620377

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The miR-363-GATA6-Lgr5 pathway is critical for colorectal tumorigenesis2014

    • Author(s)
      Tsuji S
    • Journal Title

      Nat. Commun.

      Volume: 5 Issue: 1 Pages: 3150-3150

    • DOI

      10.1038/ncomms4150

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differences in the localization of the APC-Asef/Asef2 complex between APC wild-type and mutant cells2013

    • Author(s)
      Yoshihiro Kawasaki, Shiori Furukawa, Rina Sato, Tetsu Akiyama
    • Journal Title

      Cancer Sci.

      Volume: 8 Issue: 8 Pages: 1135-1138

    • DOI

      10.1111/cas.12180

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The miR-1-NOTCH3-Asef Pathway Is Important for Colorectal Tumor Cell Migration2013

    • Author(s)
      Shiori Furukawa,Yoshihiro Kawasaki, Masaya Miyamoto, Masaya Hiyoshi,Joji Kitayama, Tetsu Akiyama
    • Journal Title

      PLoS ONE

      Volume: 8 Issue: 11 Pages: e80609-e80609

    • DOI

      10.1371/journal.pone.0080609

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] MYU, a novel target lncRNA for Wnt/c-Myc signaling, mediates CDK6 induction to promote cell cycle progression2015

    • Author(s)
      Kawasaki Y, Akiyama T.
    • Organizer
      第74回日本癌学会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] The Achilles' heel of cancers.2015

    • Author(s)
      Kawasaki Y, Akiyama T.
    • Organizer
      International Symposium on “Integrative Research on Cancer Microenvironment Network”
    • Place of Presentation
      東京大学小柴ホール(東京都文京区)
    • Year and Date
      2015-09-11
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] MYU, a novel target lncRNA for Wnt/c-Myc signaling, mediates CDK6 induction to promote cell cycle progression2015

    • Author(s)
      Kawasaki Y, Akiyama T
    • Organizer
      Joint International Symposium on TGF-β Family and Cancer: TGF-β Family and Cancer: Signal Network in Tumor Micoroenvironment
    • Place of Presentation
      筑波
    • Year and Date
      2015-01-12 – 2015-01-13
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] GATA6を介した細胞癌化におけるReg4とLgr5の協調作用2014

    • Author(s)
      川崎善博、辻真之介、宮本昌弥、平岡巧士、松村厚佑、奥野ます美、須田咲希子、日吉雅也、北山丈二、秋山徹
    • Organizer
      日本分子生物学会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 大腸がん幹細胞における新規長鎖非コードRNAの機能解析2014

    • Author(s)
      松村厚佑、宮本昌弥、川崎善博、斎藤晋祐、日吉雅也、北山丈二、秋山徹
    • Organizer
      日本分子生物学会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Cooperation between Reg4 and Lgr5 in GATA6-mediated colorectal tumorigenesis2014

    • Author(s)
      川崎善博、辻真之介、宮本昌弥、平岡巧士、松村厚佑、奥野ます美、須田咲希子、日吉雅也、北山丈二、秋山徹
    • Organizer
      日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] The role of the novel long non-coding RNA in human colorectal cancer stem cell2014

    • Author(s)
      松村厚佑、宮本昌弥、川崎善博、斎藤晋祐、日吉雅也、北山丈二、秋山徹
    • Organizer
      日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] The role of miR-363-GATA6-Lgr5 pathway in colorectal tumorigenesis2013

    • Author(s)
      川崎 善博、辻 真之介、古川 史織、谷上 賢瑞、林 寛敦、日吉 雅也 、北山 丈二 、秋山 徹
    • 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
  • [Book] 日本臨床 微小環境を標的とした分子標的治療2015

    • Author(s)
      川崎善博, 秋山徹
    • Total Pages
      5
    • Publisher
      日本臨床社
    • Related Report
      2015 Annual Research Report
  • [Book] サイトカイン・増殖因子キーワード事典2015

    • Author(s)
      川崎善博
    • Publisher
      羊土社
    • Related Report
      2014 Annual Research Report

URL: 

Published: 2013-05-21   Modified: 2019-07-29  

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