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Elucidation of the molecular mechanisms by which DPP-4 plays a role in the development and metastasis of malignant tumors

Research Project

Project/Area Number 18K16214
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54040:Metabolism and endocrinology-related
Research InstitutionKanazawa Medical University

Principal Investigator

TAKAGAKI Yuta  金沢医科大学, 医学部, 助教 (50759123)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords糖尿病 / DPP-4 / 癌 / 乳癌 / 上皮間葉系細胞分化 / CXCL12/CXCR4 / mTOR / インクレチン / EMTプログラム
Outline of Final Research Achievements

In vitro, DPP-4 inhibitor treatment induced EMT program by activating mTOR in a CXCL12/CXCR4 signaling-dependent manner, and in vivo, CXCR4 inhibitor treatment reduced tumor size and suppressed metastasis. In addition, DPP-4 knockdown breast cancer cells acquired resistance to doxorubicin through induction of the EMT program. Using surgical specimens, we found that DPP-4 expression was increased and CXCR4 expression was decreased in Stage I breast cancer tissues, while DPP-4 expression was decreased and CXCR4 expression was increased in Stage IV breast cancer tissues.

Academic Significance and Societal Importance of the Research Achievements

糖尿病患者は癌のリスクが上昇することが知られており、2倍以上リスクが増加する癌種もあり、糖尿病治療薬により発癌、病期進行を来す可能性に関しては十分な検討が必要である。本研究の結果は現在、その優れた血糖降下作用や低血糖リスクの少なさから、高齢者を含めた多くの患者に使用されている、DPP-4阻害薬の新たなリスクの可能性を明らかにすることで、より病態に応じた使い分けを行う指標となる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (3 results)

All 2019 2018

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

  • [Journal Article] Inhibition of Dipeptidyl Peptidase-4 Accelerates Epithelial?Mesenchymal Transition and Breast Cancer Metastasis via the CXCL12/CXCR4/mTOR Axis2018

    • Author(s)
      Yang Fan、Takagaki Yuta、Yoshitomi Yasuo、Ikeda Takayuki、Li Jinpeng、Kitada Munehiro、Kumagai Asako、Kawakita Emi、Shi Sen、Kanasaki Keizo、Koya Daisuke
    • Journal Title

      Cancer Research

      Volume: 79 Issue: 4 Pages: 735-746

    • DOI

      10.1158/0008-5472.can-18-0620

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] メトホルミンとDPP-4阻害薬の併用が乳癌細胞の肺転移に与える影響についての検討2019

    • Author(s)
      川北恵美、熊谷麻子、高垣雄太、金崎啓造、古家大祐
    • Organizer
      第34回日本糖尿病合併症学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Dipeptidyl peptidase-4 inhibition may accelerates cancer metastasis via SDF-1/CXCR4 pathway dependent epithelial-mesenchymal transition2018

    • Author(s)
      Yuta Takagaki, FanYang, Keizo Kanasaki, Daisuke Koya
    • Organizer
      the 2018 Asia Islet Biology & Incretin Symposium
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2022-01-27  

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