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The development of novel molecularly target therapy against melanomas by targeting NUAK2

Research Project

Project/Area Number 18K08264
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53050:Dermatology-related
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Namiki Takeshi  東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (50401352)

Co-Investigator(Kenkyū-buntansha) 河上 裕  国際医療福祉大学, 医学部, 教授 (50161287)
西村 栄美  東京医科歯科大学, 難治疾患研究所, 教授 (70396331)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords悪性黒色腫
Outline of Final Research Achievements

We have already shown that AMP-related kinase NUAK2 participates in the development and progression of acral melanomas. In this study, we identified mTOR pathway, as a pathway of NUAK2 target, in melanoma cells by comprehensive gene expression analysis using microarray. We further examined downstream pathways of mTOR in detail. We also examined the effect of metformin, as a drug inhibiting NUAK2 functions, on the suppression of the proliferation of melanoma cells. We generated a transgenic mouse with melanocytes in which NUAK2 was expressed and examined an increased cell number of melanocytes.

Academic Significance and Societal Importance of the Research Achievements

本研究成果では、末端黒子型悪性黒色腫の予後と強く相関する遺伝子でもあるNUAK2の悪性黒色腫細胞増殖に働く機序につき解明を進め、NUAK2がmTORを制御することにより悪性黒色腫細胞増殖に働くことを示した。さらにNUAK2を標的とした新規分子標的治療開発のために必須となる色素細胞にNUAK2を強制発現させたトランスジェニックマウスを作製。その解析を進めた。本邦において悪性黒色腫の約半数は末端黒子型悪性黒色腫が占めており、有効な新規治療の開発を進めることは重要な社会的意義を有るものと考えられる。

Report

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

    (3 results)

All 2018

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

  • [Journal Article] 末端黒子型悪性黒色腫発症の分子機構解明と分子標的治療開発2018

    • Author(s)
      並木 剛
    • Journal Title

      加齢皮膚医学セミナー

      Volume: 13 Pages: 35-40

    • NAID

      40022279786

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] NUAK2 promotes melanoma development by regulating mTOR pathway2018

    • Author(s)
      Namiki T, Matsumura H, Yaguchi T, Kawakami Y, Nishimura EK, Yokozeki H
    • Organizer
      International Investigative Dermatology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of novel therapeutics targeting NUAK2 against acral melanomas2018

    • Author(s)
      Namiki T
    • Organizer
      The 75th Annual Meeting of the Japanese Cancer Association
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited

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Published: 2018-04-23   Modified: 2022-12-28  

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