The elucidation of melanomagenesis and the identification of cancer stem cell in early melanomas

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17342
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Nihida Makiko 東京医科歯科大学, 大学院医歯学総合研究科, 特任講師 (10736797)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 悪性黒色腫

Outline of Final Research Achievements

We have already shown that both NUAK2 and PTEN 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. We performed a screening of kinase inhibitors and biguanides for the suppression of cell proliferation of melanoma cells, and further examined the effect of metformin. We generated a transgenic mouse with melanocytes in which NUAK2 was expressed and examined an increased cell number of melanocytes.

Free Research Field

皮膚科学

Academic Significance and Societal Importance of the Research Achievements

本研究成果では、NUAK2とPTENの悪性黒色腫細胞増殖に対する機序につき解明を進め、マイクロアレイを用いた網羅的遺伝子解析によりNAUK2により制御されるパスウェイとしてmTORを特定。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。悪性黒色腫の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。