• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

BMP-4 as a new therapeutic target in colorectal cancer

Research Project

Project/Area Number 15K08393
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionThe University of Tokyo

Principal Investigator

Ehata Shogo  東京大学, 大学院医学系研究科(医学部), 特任准教授 (90506726)

Research Collaborator Yokoyama Yuichiro  東京大学, 大学院医学系研究科, 特任研究員
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsColorectal cancer / Apoptosis / BMP-4 / Erk MAPK / DUSP5 / 大腸癌 / アポトーシス / Erk / TGF-beta/BMP
Outline of Final Research Achievements

Poor prognoses for colorectal cancer patients with metastatic lesions have driven demand for the development of novel targeted therapies. Here we demonstrate that expression of bone morphogenetic protein 4 (BMP-4) is universally upregulated in human colorectal cancer cells and tissues, resulting in activated BMP signaling. Inhibition of endogenous BMP signaling by the BMP type I receptor inhibitor LDN-193189 elevated expression of the phosphatase DUSP5 in colorectal cancer cells, inducing apoptosis via dephosphorylation of Erk MAPK. Administering LDN-193189 to mice diminished tumor formation of colorectal cancer cells. Our findings suggest inhibition of autocrine BMP-4 as a candidate treatment strategy for colorectal cancer.

Report

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

    (14 results)

All 2017 2016 2015 Other

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 5 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Int'l Joint Research: 2 results) Remarks (1 results)

  • [Journal Article] Autocrine BMP-4 Signaling Is a Therapeutic Target in Colorectal Cancer2017

    • Author(s)
      Yokoyama Y, Watanabe T, Tamura Y, Hashizume Y, Miyazono K, Ehata S.
    • Journal Title

      Cancer Research

      Volume: 77 Issue: 15 Pages: 4026-4038

    • DOI

      10.1158/0008-5472.can-17-0112

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Whole-Body Profiling of Cancer Metastasis with Single-Cell Resolution2017

    • Author(s)
      Kubota Shimpei I.、Takahashi Kei、Nishida Jun、Morishita Yasuyuki、Ehata Shogo、Tainaka Kazuki、Miyazono Kohei、Ueda Hiroki R.
    • Journal Title

      Cell Reports

      Volume: 20 Issue: 1 Pages: 236-250

    • DOI

      10.1016/j.celrep.2017.06.010

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] RNA-binding motif protein 47 inhibits Nrf2 activity to suppress tumor growth in lung adenocarcinoma2016

    • Author(s)
      Sakurai T, Isogaya K, Sakai S, Morikawa M, Morishita Y, Ehata S, Miyazono K, Koinuma D
    • Journal Title

      Oncogene

      Volume: 35 Issue: 38 Pages: 5000

    • DOI

      10.1038/onc.2016.35

    • URL

      https://pure.teikyo.jp/en/publications/75c50a98-5439-4d3b-a168-ce1b38bca455

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ras and TGF-β signaling enhance cancer progression by promoting the ΔNp63 transcriptional program2016

    • Author(s)
      Vasilaki E, Morikawa M, Koinuma D, Mizutani A, Hirano Y, Ehata S, Sundqvist A, Kawasaki N, Cedervall J, Olsson AK, Aburatani H, Moustakas A, Miyazono K, Heldin CH.
    • Journal Title

      Sci Signal.

      Volume: 9 Issue: 442

    • DOI

      10.1126/scisignal.aag3232

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] EZH2 promotes progression of small cell lung cancer by suppressing the TGF-β-Smad-ASCL1 pathway2015

    • Author(s)
      Fumihiko Murai, Daizo Koinuma, Aya Shinozaki-Ushiku, Masashi Fukayama, Kohei Miyaozono, Shogo Ehata
    • Journal Title

      Cell Discovery

      Volume: 1 Issue: 1 Pages: 15026-15026

    • DOI

      10.1038/celldisc.2015.26

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] BMP阻害剤を応用した大腸がんの分子標的治療2017

    • Author(s)
      江幡正悟、横山雄一郎、宮園浩平
    • Organizer
      第21回日本がん分子標的治療学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Autocrine bone morphogenetic protein 4 signaling in colorectal cancer as a target for treatment.2017

    • Author(s)
      Ehata S, Yokoyama Y, Watanabe T, Tamura Y, Hashizume Y, Miyazono K.
    • Organizer
      FASEB “The TGF-beta Superfamily: Signaling in Development and Disease”
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] BMP阻害剤を使用した大腸癌治療の試み2017

    • Author(s)
      江幡正悟、横山雄一郎、渡邉聡明、田村佑介、宮園浩平
    • Organizer
      第76回日本癌学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Autocrine BMP-4 accelerates proteasomal degradation of Bim and protects colorectal cancer cells from apoptosis2016

    • Author(s)
      Yuichiro Yokoyama, Shogo Ehata, Toshiaki Watanabe, Kohei Miyazono
    • 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] Autocrine BMP-4 is a novel therapeutic target for colorectal cancer2016

    • Author(s)
      Yuichiro Yokoyama, Shogo Ehata, Yasuyuki Morishita, Toshiaki Watanabe, Kohei Miyazono
    • Organizer
      第10回日米癌合同会議
    • Place of Presentation
      Maui, United States of America
    • Year and Date
      2016-02-18
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Autocrine BMP-4 accelerates proteasomal degradation of Bim and protects colorectal cancer cells from apoptosis2015

    • Author(s)
      Yuichiro Yokoyama, Shogo Ehata, Toshiaki Watanabe, Kohei Miyazono
    • Organizer
      第74回日本癌学会総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-10-09
    • Related Report
      2015 Research-status Report
  • [Presentation] Autocrine BMP-4 protects colorectal cancer cells from apoptosis through down-regulation of Bim2015

    • Author(s)
      横山雄一郎、江幡正悟、渡邉聡明、宮園浩平
    • Organizer
      平成27年度がん若手研究者ワークショップ
    • Place of Presentation
      蓼科グランドホテル滝の湯(長野県茅野市)
    • Year and Date
      2015-09-03
    • Related Report
      2015 Research-status Report
  • [Presentation] 大腸癌細胞はBMP-4を自己分泌しBimタンパクの分解を促進することでアポトーシスを抑制する2015

    • Author(s)
      横山雄一郎、江幡正悟、宮園浩平
    • Organizer
      第19回日本がん分子標的治療学会学術集会
    • Place of Presentation
      松山全日空ホテル(愛媛県松山市)
    • Year and Date
      2015-06-12
    • Related Report
      2015 Research-status Report
  • [Remarks] 東京大学大学院医学系研究科病因・病理学専攻分子病理学分野 ホームページ

    • URL

      http://beta-lab.umin.ac.jp/

    • Related Report
      2015 Research-status Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi