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Fluctuation of ectodomain shedding and the emersion of cancer cell heterogeneity

Research Project

Project/Area Number 16K15221
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field General medical chemistry
Research InstitutionEhime University

Principal Investigator

Higashiyama Shigeki  愛媛大学, プロテオサイエンスセンター, 教授 (60202272)

Co-Investigator(Renkei-kenkyūsha) NAKAYAMA HIROINAO  愛媛大学, プロテオサイエンスセンター, 助教 (40512132)
Research Collaborator FUKUDA SHINJI  愛媛大学, プロテオサイエンスセンター, 講師 (70398238)
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsがん細胞の不均一性 / 乳がん細胞 / ゆらぎ / EGFファミリー / エクトドメイン・シェディング / amphiregulin / CUL3 / RhoA / 膜型細胞増殖因子 / Amphiregulin / エクトドメイン・シェディング” / アクチンダイナミクス / cullin3 / ユビキチンE3リガーゼシ / proHB-EGF / proamphiregulin / シェディング / ADAM
Outline of Final Research Achievements

Cancer is derived a single cell and becomes to show heterogeneous population during the growth of its mass in general, which seems to lead to drug resistance. The epidermal growth factor (EGF) family are transmembrane growth factors and their ectodomain shedding is a crucial event to determine their soluble growth factor levels. We speculate that the fluctuation of the ectodomain shedding of the EGF family would be related to the emersion of heterogeneous population of cancer. In this study, we at first established three clones, stem, basal and luminal types, form human breast cancer cell line, MCF-7 cells, and then performed quantitative analysis of the ectodomain shedding of EGF family ligands in these clones. We revealed that the ectodomain shedding of proAREG uniquely showed the correlation between the shedding level and clone types, and was regulated through actin dynamics by CUL3 -RING based E3 ubiquitin ligase-dependent Rho activation.

Report

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

    (10 results)

All 2018 2017 2016 Other

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

  • [Int'l Joint Research] ETH Zurich,(Switzerland)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] RWTH Aachen University, Aachen/Christian-Albrechts-University, Kiel(Germany)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] University of Liege and CHU Liege, Liege(Belgium)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Cullin 3 regulates ADAMs-mediated ectodomain shedding of amphiregulin2018

    • Author(s)
      Nakayama Hironao、Sakaue Tomohisa、Maekawa Masashi、Fujisaki Ayako、Higashiyama Shigeki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 499 Issue: 1 Pages: 17-23

    • DOI

      10.1016/j.bbrc.2018.03.097

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glutamate-Dependent Ectodomain Shedding of Neuregulin-1 Type II Precursors in Rat Forebrain Neurons.2017

    • Author(s)
      1)Iwakura Y, Wang R, Inamura N, Araki K, Higashiyama S, Takei N, Nawa N
    • Journal Title

      PLoS One

      Volume: 12 Issue: 3 Pages: e0174780-e0174780

    • DOI

      10.1371/journal.pone.0174780

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Stimulated release and functional activity of surface expressed metalloproteinase ADAM17 in exosomes.2016

    • Author(s)
      Groth E, Pruessmeyer J, Babendreyer A, Schumacher J, Pasqualon T, Dreymueller D, Higashiyama S, Lorenzen I, Grotzinger J, Cataldo D, Ludwig A.
    • Journal Title

      Biochim Biophys Acta.

      Volume: 1863 Issue: 11 Pages: 2795-2808

    • DOI

      10.1016/j.bbamcr.2016.09.002

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ectodomain Shedding of Lymphatic Vessel Endothelial Hyaluronan Receptor 1 (LYVE-1) is induced by VEGF-A.2016

    • Author(s)
      Nishida-Fukuda H, Araki R, Shudou M, Okazaki H, Tomono Y, Nakayama H, Fukuda S, Sakaue T, Shirakata Y, Sayama K, Hashimoto K, Detmar M, Higashiyama S, Hirakawa S.
    • Journal Title

      J Biol Chem.

      Volume: 291 Issue: 20 Pages: 10490-10490

    • DOI

      10.1074/jbc.m115.683201

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] EGFファミリー分子のshedding特性解析2016

    • Author(s)
      中山寛尚, 坂上倫久, 前川大志, 藤崎亜耶子, 東山繁樹
    • Organizer
      第57回日本生化学会中国・四国支部例会
    • Place of Presentation
      高知
    • Year and Date
      2016-05-27
    • Related Report
      2016 Research-status Report
  • [Remarks] 愛媛大学プロテオサイエンスセンター 細胞増殖・腫瘍制御部門

    • URL

      https://www.m.ehime-u.ac.jp/school/biochem2/

    • Related Report
      2017 Annual Research Report
  • [Remarks] Proteo-Science (PROS), Ehime University

    • URL

      http://www.m.ehime-u.ac.jp/school/biochem2/

    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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