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

• Project/Area Number: 18K08264
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Tokyo 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: ¥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。

Research Products

• [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
  • Peer Reviewed
• [Presentation] NUAK2 promotes melanoma development by regulating mTOR pathway (2018)
  • Author(s): Namiki T, Matsumura H, Yaguchi T, Kawakami Y, Nishimura EK, Yokozeki H
  • Organizer: International Investigative Dermatology
  • Int'l Joint Research
• [Presentation] Development of novel therapeutics targeting NUAK2 against acral melanomas (2018)
  • Author(s): Namiki T
  • Organizer: The 75th Annual Meeting of the Japanese Cancer Association
  • Int'l Joint Research / Invited