Functional analysis of the inhibitor for epithelial-mesenchymal transition on oral cancer stem cells towards the development of new cancer treatments

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K10274
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Tokyo Medical University
• Principal Investigator: Watanabe Masato 東京医科大学, 医学部, 兼任准教授 (40349460)
• Co-Investigator(Kenkyū-buntansha): 河野 通秀 東京医科大学, 医学部, 講師 (00421066) ; 古賀 陽子 東京医科大学, 医学部, 兼任教授 (10392408) ; 近津 大地 東京医科大学, 医学部, 主任教授 (30343122)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 口腔扁平上皮癌 / がん幹細胞 / 上皮間葉転換 / ユビキチンリガーゼ / microRNA

Outline of Final Research Achievements

The success or failure of cancer treatment is characterized by the resistance of cancer stem cells to therapy. Elucidating epithelial-mesenchymal transition, which is considered to be one of the characteristics of cancer stem cells, will provide clues for controlling drug sensitivity. Therefore, we attempted to identify epithelial-mesenchymal transition stem cells from oral squamous cell carcinoma tissue and to elucidate the presence of ubiquitin ligase (Fbxw7), an epithelial-mesenchymal transition inhibitor. This study examines the negative effect of Fbxw7 on epithelial-mesenchymal transition at a basic level. As a result, epithelial-mesenchymal transition type stem cells were speculated at the tissue level, however their characteristics, drug resistance or significant negative effects of Fbxw7 on epithelial-mesenchymal transition were unknown. There were no molecular biomarkers targeted to Fbxw7.

Free Research Field

口腔腫瘍

Academic Significance and Societal Importance of the Research Achievements

本研究の特色として、抗腫瘍性の直接的な新規薬物開発に関連するものではない。がん幹細胞の薬剤抵抗性に焦点をあて、いかにがん幹細胞の感受性を高めるかその因子の解明あるいはそれに関連したバイオマーカーの解明を試みた研究である。これまでの抗がん剤あるいは分子標的剤は各増殖期に相応し効果を発揮するが、感受性が低いG0期のがん幹細胞は対象外であった。その為、G0期へ移行を阻止する因子の解明は、薬物療法を補完する観点で興味深い研究であった。