The identification of cancer stem cell in acral melanoma and the development of a novel molecularly target therapy

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17763
• 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: Yoshioka Yusuke 東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (00835770)
• Project Period (FY): 2019-04-01 – 2021-03-31
• 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 analyzed signaling pathways of both LKB1-AMPKs and DKK1-WNT/b-catenin in acral melanoma cells, explored cancer stem cells of acral melanoma using clinical specimens, and attempted to identify an inhibitor targeting NUAK2 pathways. The results of this study can be a foundation for both exploration of acral melanomagenesis and the development of a novel molecularly target therapy.

Free Research Field

悪性黒色腫

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内におけるLKB1-AMPKs系とNUAK2のシグナル伝達路の相互関係につき解析を進め、NUAK2が末端黒子型悪性黒色腫において掌蹠の汗腺線体部に発現されていることを確認。さらにAMPK-NUAK2系を阻害して細胞増殖を抑制する作用のある薬剤としてメトホルミンにつき検討を加えた。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。