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Investigation of DYRK2 downstream gene in breast cancer to elucidate the mechanisms of tumor growth and invasion

Research Project

Project/Area Number 18K16267
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 55010:General surgery and pediatric surgery-related
Research InstitutionThe University of Tokyo (2022)
Jikei University School of Medicine (2018-2021)

Principal Investigator

Imawari Yoshimi  東京大学, 医科学研究所, 特任助教 (20649040)

Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
KeywordsDYRK2 / 乳癌 / 腫瘍増殖 / CDK14
Outline of Final Research Achievements

Tumor progression is the main cause of death in patients with breast cancer. Accumulating evidence suggests that dual-specificity tyrosine-regulated kinase 2 (DYRK2) functions as a tumor suppressor by regulating cell survival, differentiation, proliferation and apoptosis. However, little is known about the mechanisms of transcriptional regulation by DYRK2 in cancer progression, particularly with respect to cancer proliferation and invasion.
Here, using a comprehensive expression profiling approach, we show that cyclin-dependent kinase 14 (CDK14) is a target of DYRK2. We further identified androgen receptor (AR) as a candidate of DYRK2-dependent transcription factors regulating CDK14.
Our findings demonstrate that reduced DYRK2 expression in breast cancer promotes tumor cell proliferation and invasion by modulating CDK14 expression via AR, and inhibits the growth by treatment with AR inhibitor, MDV3100.

Academic Significance and Societal Importance of the Research Achievements

本研究では、乳癌におけるDYRK2によるCDK14の発現制御機構を解明し、更にDYRK2の発現が低い乳癌に対して、治療効果が期待出来る化合物を同定した。
臨床検体を用いた病理解析も併せて行ったことで、基礎研究での成果を臨床での「DYRK2の発現の低い、すなわち悪性度の高い乳癌に特異的な治療法の確立」へと繋げる架け橋のような知見を見出すことが出来たと考える。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (15 results)

All 2022 2021 2020 2019 2018 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (9 results) (of which Int'l Joint Research: 2 results) Remarks (3 results)

  • [Journal Article] Molecular Targeted Therapy for Hormone Receptor-Positive, Human Epidermal Growth Factor 2-Negative Metastatic Breast Cancer in Clinical Practice2022

    • Author(s)
      Nakano S.、Imawari Y.、Mibu A.、Kato S.、Yamaguchi S.、Otsuka M.、Sano M.
    • Journal Title

      Journal of Nippon Medical School

      Volume: 89 Issue: 1 Pages: 88-94

    • DOI

      10.1272/jnms.JNMS.2022_89-203

    • NAID

      130008027458

    • ISSN
      1345-4676, 1347-3409
    • Year and Date
      2022-02-25
    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Downregulation of dual-specificity tyrosine-regulated kinase 2 promotes tumor cell proliferation and invasion by enhancing cyclin-dependent kinase 14 expression in breast cancer2018

    • Author(s)
      Imawari Yoshimi、Mimoto Rei、Hirooka Shinichi、Morikawa Toshiaki、Takeyama Hiroshi、Yoshida Kiyotsugu
    • Journal Title

      Cancer Science

      Volume: 109 Issue: 2 Pages: 363-372

    • DOI

      10.1111/cas.13459

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differentiating vacuum-assisted breast biopsy from core needle biopsy: Is it necessary?2018

    • Author(s)
      Nakano Satoko、Imawari Yoshimi、Mibu Akemi、Otsuka Masahiko、Oinuma Toshinori
    • Journal Title

      The British Journal of Radiology

      Volume: 91 Issue: 1092

    • DOI

      10.1259/bjr.20180250

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 同一腫瘤内に乳管癌と小葉癌が混在した乳癌の一症例2022

    • Author(s)
      井廻良美,三宅亮,三宅美佐代,野木裕子
    • Organizer
      第30回日本乳癌学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 腋窩リンパ節腫大を伴った乳腺顆粒細胞腫の 1 例2022

    • Author(s)
      三宅亮,井廻良美,武山浩,野木裕子
    • Organizer
      第30回日本乳癌学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] MDV3100はホルモン受容体陽性HER2陰性DYRK2低発現乳癌細胞株において有効である2021

    • Author(s)
      井廻良美,三本麗,野木裕子,鳥海弥寿雄,武山浩
    • Organizer
      第29回日本乳癌学会学術総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 内分泌療法後に第5次治療でCDK4/6阻害剤を使用し8ヶ月間以上の奏功が得られた転移再発乳癌の1症例2020

    • Author(s)
      井廻良美,中野聡子,壬生明美,生沼利倫
    • Organizer
      第28回日本乳癌学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 無石胆嚢炎を併発した同時両側乳癌、胆嚢転移の1症例2019

    • Author(s)
      井廻良美,中野聡子,加藤俊介,山口茂夫,壬生明美,生沼利倫
    • Organizer
      第27回日本乳癌学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Downregulation of DYRK2 contributes to tumor cell proliferation by enhancing CDK14 expression in breast cancer2019

    • Author(s)
      Yoshimi Imawari, Rei Mimoto, Noriko Yamaguchi, Makiko Kamio, Hiroko Nogi, Ken Uchida, Hiroshi Takeyama, Kiyotsugu Yoshida
    • Organizer
      the 42nd Annual San Antonio Breast Cancer Symposium
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] DYRK2 contributes to the tumor cell proliferation and invasion through CDK14 in breast cancer cells2019

    • Author(s)
      Yoshimi Imawari, Rei Mimoto, Noriko Yamaguchi, Hiroshi Takeyama, Kiyotsugu Yoshida
    • Organizer
      Eleventh AACR-JCA Joint Conference on Breakthroughs in Cancer Research: Biology to Precision Medicine
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 乳癌においてDYRK2はCDK14を介して腫瘍増殖を制御する2018

    • Author(s)
      井廻良美,三本麗,風間高志,野木裕子,塩谷尚志,木下智樹,鳥海弥寿雄,内田賢,武山浩
    • Organizer
      第26回日本乳癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 乳癌細胞株においてDYRK2はCDK14を介して腫瘍増殖を制御する2018

    • Author(s)
      井廻良美,三本麗,山口乃里子,武山浩,吉田清嗣
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Remarks] 東京大学大学院 理学系研究科 癌防御シグナル分野 中西研究室

    • URL

      https://www.ims.u-tokyo.ac.jp/cancer-cell-biology/hp2018/01index.html

    • Related Report
      2022 Annual Research Report
  • [Remarks] 東京慈恵会医科大学 生化学講座 吉田研究室

    • URL

      http://jikei-biochem.wixsite.com/yoshidalab

    • Related Report
      2021 Research-status Report 2020 Research-status Report 2019 Research-status Report
  • [Remarks] 東京慈恵会医科大学 生化学講座 吉田研究室

    • URL

      http://jikei-biochem.wixsite.com/yoshidalab

    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2024-01-30  

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