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Roles and mechanisms of inhibitory Smads in the regulation of breast cancer stem cells

Research Project

Project/Area Number 16K20974
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Tumor biology
General medical chemistry
Research InstitutionThe University of Tokyo

Principal Investigator

AKAGI Yoko  東京大学, 大学院医学系研究科(医学部), 助教 (70771004)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsTGF-beta / 上皮間葉移行 / がん幹細胞 / PRMT1 / 抑制型Smad / EMT / Smad / cancer stem cell / シグナル伝達 / 癌
Outline of Final Research Achievements

Tumors are composed of different cell types including cancer stem cells (CSCs), their heterogeneous progeny and the stromal cells. In contrast to classical model of CSC differentiation, epithelial cancer cells are now considered to have differentiation plasticity. Understanding the signaling networks that control the differentiation plasticity is essential to target cancer cells.
The epithelial-to-mesenchymal transdifferentiation (EMT) is an essential process in development, and is reactivated in cancer cells to promote invasion, contribute to cancer stroma formation, generate CSCs and decrease sensitivity to anticancer drugs. TGF-beta signaling, which is often activated in carcinomas, drives EMT of carcinoma cells.
This study provides evidence that an Arginine methyltransferase PRMT1 promotes the TGF-beta-induced EMT and epithelial stem cell generation through the methylation of Smad7. This mechanism may provide a new treatment strategy to target CSCs.

Report

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

    (7 results)

All 2017 2016 Other

All Int'l Joint Research (2 results) Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results) Presentation (4 results) (of which Int'l Joint Research: 2 results)

  • [Int'l Joint Research] カリフォルニア大学サンフランシスコ校(米国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] カリフォルニア大学サンフランシスコ校(米国)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Smad3‐mediated recruitment of the methyltransferase SETDB1/ESET controls Snail1 expression and epithelial?mesenchymal transition2017

    • Author(s)
      Du Dan、Katsuno Yoko、Meyer Dominique、Budi Erine H、Chen Si‐Han、Koeppen Hartmut、Wang Hongjun、Akhurst Rosemary J、Derynck Rik
    • Journal Title

      EMBO reports

      Volume: 19 Issue: 1 Pages: 135-155

    • DOI

      10.15252/embr.201744250

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Prolonged exposure to TGF-β stabilizes the stem cell-like state of breast cancer cells through activation of Akt-mTOR signaling.2017

    • Author(s)
      Yoko Katsuno, Kohei Miyazono, Rik Derynck
    • Organizer
      FASEB Science Research Conference "TGF-β Superfamily: Signaling in Development and Disease"
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Prolonged exposure to TGF-β stabilizes the stem cell-like state and increases drug resistance of breast cancer cells.2017

    • Author(s)
      Yoko Katsuno, Kohei Miyazono, Rik Derynck
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Prolonged exposure to TGF-beta stabilizes stem-cell state of breast cancer cells through activation of Akt signaling.2016

    • Author(s)
      Yoko Katsuno, Kohei Miyazono, Rik Derynck
    • 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] Regulation of epithelial plasticity and differentiation of breast cancer cells by TGF-beta2016

    • Author(s)
      Yoko Katsuno
    • Organizer
      TGF-beta Signaling LCR Meeting Leiden
    • Place of Presentation
      ライデン(オランダ)
    • Year and Date
      2016-08-21
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2022-06-07  

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