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Novel mechanism(s) of stemness regulation mediated by oncogenes

Research Project

Project/Area Number 17K08626
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General medical chemistry
Research InstitutionKanazawa University

Principal Investigator

Akagi Tadayuki  金沢大学, 医学系, 准教授 (70532183)

Co-Investigator(Kenkyū-buntansha) 横田 崇  金沢大学, 医学系, 協力研究員 (50134622)
上田 篤  金沢大学, 医学系, 助教 (90728560)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords多能性幹細胞 / がん遺伝子 / 転写因子 / 遺伝子発現 / ES細胞 / ES細胞 / 自己複製 / 多分化能
Outline of Final Research Achievements

Pluripotent stem cells, including mouse embryonic stem cells (ES cells) have self-renewal ability and pluripotency. The self-renewal ability of mouse ES cells is maintained by stimulation with the cytokine LIF followed by activation of the transcription factor STAT3. Several investigators, including us, have been working to elucidate the molecular basis of the self-renewal mechanism using STAT3 and its related transcription factors. Interestingly, it has been pointed out that ES cells have similarities with cancer cells. Recent studies have also reported various mutant STAT3 in human cancer tissues. In this study, we focus on the mutant STAT3 which is found in cancer cells and aims to elucidate a novel mechanism(s) of self-renewal regulation mediated by oncogenes.

Academic Significance and Societal Importance of the Research Achievements

変異型STAT3をES細胞に過剰発現させると、LIF非依存的な自己複製が観察された。これらの細胞はLIF非存在下でアルカリフォスファターゼ陽性で、未分化マーカー遺伝子の発現も認められた。変異型STAT3の機能は、STAT3遺伝子破壊ES細胞でも観察できた。さらに興味深いことに、変異型STAT3はLIF非存在下でES細胞の増殖能を促進する機能があることを見出した。このことから、変異型STAT3はLIFに依存することなく、ES細胞の自己複製を維持する機能が示された。これは、がん細胞で認められる遺伝子発現制御機構をES細胞内で再構築することで、ES細胞の幹細胞性を模倣できている可能性を示唆する。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (19 results)

All 2019 2018 2017 Other

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (13 results) (of which Int'l Joint Research: 4 results) Remarks (3 results)

  • [Journal Article] Baf53a is involved in survival of mouse ES cells, which can be compensated by Baf53b2017

    • Author(s)
      Zhu Bo、Ueda Atsushi、Song Xiaohong、Horike Shin-ichi、Yokota Takashi、Akagi Tadayuki
    • Journal Title

      Sci Rep.

      Volume: 7 Issue: 1

    • DOI

      10.1038/s41598-017-14362-4

    • NAID

      120006375099

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] GA-Binding Protein Alpha Is Involved in the Survival of Mouse Embryonic Stem Cells2017

    • Author(s)
      Ueda Atsushi、Akagi Tadayuki、Yokota Takashi
    • Journal Title

      Stem Cells

      Volume: 35 Issue: 11 Pages: 2229-2238

    • DOI

      10.1002/stem.2673

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Copy number analysis identifies tumor suppressive lncRNAs in human osteosarcoma2017

    • Author(s)
      Xie Jianjun、Lin Dechen、Lee Dhong Hyun Tony、Akunowicz Jennifer、Hansen Marc、Miller Carl、Sanada Masashi、Kato Motohiro、Akagi Tadayuki、Kawamata Norihiko、Ogawa Seishi、Koeffler H. Phillip
    • Journal Title

      Int J Oncol

      Volume: 50 Issue: 3 Pages: 863-872

    • DOI

      10.3892/ijo.2017.3864

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] がん細胞で認められた変異型STAT3を介した多能性幹細胞の自己複製制御機構2019

    • Author(s)
      赤木紀之、上田篤、手塚聡、増田涼香、下崎琳、堀家慎一、渡会浩志、横田崇
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] マウスES細胞におけるEtsファミリー転写因子GABPの各構成因子の役割2019

    • Author(s)
      上田篤、赤木紀之、堀家慎一、渡会浩志、横田崇
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Molecular mechanisms of self-renewal ability and pluripotency of stem cells.2019

    • Author(s)
      赤木紀之
    • Organizer
      第1回 反分野的生物医療学会/Anti-disciplinary Biomedical Scientific Symposium.
    • Related Report
      2019 Annual Research Report
  • [Presentation] マウスES細胞における転写因子GABPの機能解析.2018

    • Author(s)
      上田篤、赤木紀之、横田崇.
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] がん遺伝子を介した胚性幹細胞(ES細胞)の自己複製制御機構の解析2018

    • Author(s)
      赤木紀之
    • Organizer
      北陸エピジェネティクス研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] STAT3 S727 リン酸化の未分化ES 細胞における役割の解析2018

    • Author(s)
      手塚聡
    • Organizer
      生化学会若手の会 第58回 生命科学夏の学校
    • Related Report
      2018 Research-status Report
  • [Presentation] 緑色蛍光タンパク質を利用した転写因子STAT3の細胞内局在の検討2018

    • Author(s)
      増田涼香、下﨑琳.
    • Organizer
      平成30年度 関東研究医養成コンソーシアム 第9回夏のリトリート
    • Related Report
      2018 Research-status Report
  • [Presentation] Ets-related transcription factor GABPα is involved in the survival of mouse embryonic stem cells.2017

    • Author(s)
      Atsushi Ueda, Tadayuki Akagi, Takashi Yokota.
    • Organizer
      The 5th Annual Meeting of the International Cytokine and Interferon Society
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Functional analysis of 2 amino acids deleted transcription factor C/EBP epsilon found in neutrophil-specific granule deficiency.2017

    • Author(s)
      Tadayuki Akagi, Taizo Wada, Masahiro Muraoka, Tomoko Toma, Kenzo Kaji, Kazunaga Agematsu, H. Phillip Koeffler, Akihiro Yachie, Takashi Yokota
    • Organizer
      The 5th Annual Meeting of the International Cytokine and Interferon Society
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Loss of function of Baf53a (a subunit of chromatin remodeling complex) results in cell death and Baf53b, as well as Baf53a, rescue the phenotype in mouse ES cells.2017

    • Author(s)
      Bo Zhu, Ueda Ueda, Xiaohong Song, Tadayuki Akagi, Takashi Yokota.
    • Organizer
      The 5th Annual Meeting of the International Cytokine and Interferon Society
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Baf53a is involved in proliferation of ES cells by regulating p53-p21 pathway and Baf53b compensates for Baf53a function.2017

    • Author(s)
      Bo Zhu, Atsushi Ueda, Xiaohong Song, Tadayuki Akagi, Takashi Yokota.
    • Organizer
      ISSCR 2017 Annual Meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Baf53a deficiency inhibits cell proliferation and Baf53b substitutes for functions of Baf53a in mouse embryonic stem cells2017

    • Author(s)
      Bo Zhu, Atsushi Ueda, Xiaohong Song, Tadayuki Akagi, Takashi Yokota
    • Organizer
      第15回幹細胞シンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] 好中球二次顆粒球欠損症における2アミノ酸欠損型C/EBPεの機能解析.2017

    • Author(s)
      赤木紀之、村岡正裕、和田泰三、東馬智子、加治賢三、上松一永、H. Phillip Koeffler、谷内江昭宏、横田崇.
    • Organizer
      第79回日本血液学会学術集会
    • Related Report
      2017 Research-status Report
  • [Remarks] 金沢大学 医薬保健研究域医学系 再生分子医学研究分野

    • URL

      https://sites.google.com/view/kanazawa-stemcellbiol/

    • Related Report
      2018 Research-status Report
  • [Remarks] 金沢大学 再生分子医学

    • URL

      https://www.facebook.com/stem.cell.biol/

    • Related Report
      2017 Research-status Report
  • [Remarks] 研究者情報

    • URL

      http://ridb.kanazawa-u.ac.jp/public/detail.php?id=3344&page=1&org2_cd=360200

    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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