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Molecular mechanisms of cancer stem cells for neoplastic cellular transformation

Research Project

Project/Area Number 26290041
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Tumor biology
Research InstitutionJikei University School of Medicine

Principal Investigator

YOSHIDA KIYOTSUGU  東京慈恵会医科大学, 医学部, 教授 (70345312)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2016: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Keywords癌 / 幹細胞 / 上皮間葉転換
Outline of Final Research Achievements

EMT plays a fundamental role in the early stages of cancer invasion. E-cadherin is an important regulator of EMT. We identified that DYRK2 regulates E-cadherin expression. Knockdown of DYRK2 promoted EMT and cancer invasion in vitro and in vivo.
Attenuated expression of DYRK2 promotes cancer stem-like traits in vitro, tumourigenesis in vivo, and cancer stem cell population. We found that KLF4 serves as a key molecule controlling DYRK2-mediated cancer stem cell. Reduced DYRK2 expression leads to an increase of KLF4 expression, which induces cancer stem-like properties.
We also found that mTORC1 pathway is activated in DYRK2-depleted cells. The ectopic expression of DYRK2 promoted phosphorylation for the ubiquitination and degradation of mTOR.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (15 results)

All 2017 2016 2015 2014

All Journal Article (12 results) (of which Peer Reviewed: 12 results,  Acknowledgement Compliant: 10 results,  Open Access: 2 results) Presentation (3 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] Impairment of DYRK2 augments stem-like traits by promoting KLF4 expression in breast cancer.2017

    • Author(s)
      Mimoto R, Imawari Y, Hirooka S, Takeyama H, Yoshida K.
    • Journal Title

      Oncogene

      Volume: 36 Issue: 13 Pages: 1862-1872

    • DOI

      10.1038/onc.2016.349

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Diminished DYRK2 sensitizes hormone receptor-positive breast cancer to everolimus by the escape from degrading mTOR.2017

    • Author(s)
      Mimoto R, Nihira NT, Hirooka S, Takeyama H, Yoshida K.
    • Journal Title

      Cancer Letters

      Volume: 384 Pages: 27-38

    • DOI

      10.1016/j.canlet.2016.10.015

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Crosstalk between tumor suppressors p53 and PKC: Execution of the intrinsic apoptotic pathways.2016

    • Author(s)
      Dashzeveg N, Yoshida K.
    • Journal Title

      Cancer Letters

      Volume: 377 Issue: 2 Pages: 158-163

    • DOI

      10.1016/j.canlet.2016.04.032

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Transcriptional induction of protein kinase C delta by p53 tumor suppressor in the apoptotic response to DNA damage.2016

    • Author(s)
      Dashzeveg N, Yogosawa S, Yoshida K.
    • Journal Title

      Cancer Letters

      Volume: 374 Issue: 1 Pages: 167-174

    • DOI

      10.1016/j.canlet.2016.02.012

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] DYRK2 regulates epithelial-mesenchymal-transition and chemosensitivity through Snail degradation in ovarian serous adenocarcinoma.2015

    • Author(s)
      Yamaguchi N, Mimoto R, Yanaihara N, Imawari Y, Hirooka S, Okamoto A, Yoshida K.
    • Journal Title

      Tumor Biology

      Volume: 36 Issue: 8 Pages: 5913-5923

    • DOI

      10.1007/s13277-015-3264-y

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Proteasome inhibitor-resistant cells cause EMT-induction via suppression of E-cadherin by miR-200 and ZEB1.2015

    • Author(s)
      Asakura T, Yamaguchi N, Ohkawa K, Yoshida K.
    • Journal Title

      International Journal of Oncology

      Volume: 46 Issue: 5 Pages: 2251-2260

    • DOI

      10.3892/ijo.2015.2916

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cell death decision by p53 via control of the mitochondrial membrane.2015

    • Author(s)
      Dashzeveg N, Yoshida K.
    • Journal Title

      Cancer Letters

      Volume: 367 Issue: 2 Pages: 108-112

    • DOI

      10.1016/j.canlet.2015.07.019

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Engagement of DYRK2 in proper control for cell division.2015

    • Author(s)
      Nihira NT, Yoshida K.
    • Journal Title

      Cell Cycle

      Volume: 14 Issue: 6 Pages: 802-7

    • DOI

      10.1080/15384101.2015.1007751

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Mps1 phosphorylation of condensin II controls chromosome condensation at the onset of mitosis.2014

    • Author(s)
      Kagami Y, Nihira K, Wada S, Ono M, Honda M, Yoshida K.
    • Journal Title

      J Cell Biol

      Volume: 205 Issue: 6 Pages: 781-90

    • DOI

      10.1083/jcb.201308172

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Tumor suppressor p53 induces miR-1915 processing to inhibit Bcl-2 in the apoptotic response to DNA damage.2014

    • Author(s)
      Nakazawa K, Dashzeveg N, Yoshida K.
    • Journal Title

      FEBS J

      Volume: 281 Issue: 13 Pages: 2937-44

    • DOI

      10.1111/febs.12831

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Induction of amphiregulin by p53 promotes apoptosis via control of microRNA biogenesis in response to DNA damage2014

    • Author(s)
      Taira N, Yamaguchi T, Kimura J, Lu Z-G, Fukuda S, Higashiyama S, Ono M, Yoshida K
    • Journal Title

      Proc. Natl. Acad. Sci. USA

      Volume: 111 Issue: 2 Pages: 717-722

    • DOI

      10.1073/pnas.1313675111

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Palmdelphin, a novel target of p53 with Ser46 phosphorylation, controls cell death in response to DNA damage.2014

    • Author(s)
      Dashzeveg N, Taira N, Lu ZG, Kimura J, Yoshida K.
    • Journal Title

      Cell Death Dis

      Volume: 5 Issue: 5 Pages: e1221-e1221

    • DOI

      10.1038/cddis.2014.176

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Tumor suppressive function of DYRK2.2017

    • Author(s)
      Yoshida K.
    • Organizer
      DYRK1A, related kinases and human disease.
    • Place of Presentation
      Saint Malo, France
    • Year and Date
      2017-03-28
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] DYRK2 contributes to the generation of breast cancer stem cells through KLF4.2016

    • Author(s)
      Imawari Y, Mimoto RK, Yamaguchi N, Yoshida K.
    • Organizer
      10th Joint Conference of the American Association for Cancer Research and the Japanese Cancer Association.
    • Place of Presentation
      Maui, HI
    • Year and Date
      2016-02-16
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The phosphorylation of p53 at ser46 is essential to induce cell death through palmedlphin in response to DNA damage.2015

    • Author(s)
      Dashzeveg N, Yoshida K.
    • Organizer
      AACR Annual Meeting 2015
    • Place of Presentation
      Philadelphia, PA
    • Year and Date
      2015-04-18 – 2015-04-22
    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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