Chromatin remodeling in malignant progression of head-and-neck squamous cell carcinomas

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K10080
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57020:Oral pathobiological science-related
• Research Institution: Kanagawa Dental College
• Principal Investigator: Kurata Shun-ichi 神奈川歯科大学, 歯学部, 特任教授 (60140901)
• Co-Investigator(Kenkyū-buntansha): 加藤 伊陽子 神奈川歯科大学, 歯学部, 特任教授 (20333297)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 頭頸部扁平上皮癌 / TP63

Outline of Final Research Achievements

To understand the mechanism of malignant progression of head-and-neck carcinomas, we performed genome editing targeting TP63 gene which is essential for epidermal cell differentiation. The knockout cells showed massive changes in gene expression profile characteristic to epithelial to mesenchymal transition, an event observed in cancer progression. Furthermore, DNA methylation and demethylation selectively occurred in the promoter and body of genes, indicating chromatin remodeling. These results suggest that the process of malignant progression of head-and-neck carcinomas is controlled epigenetically.

Free Research Field

分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究では頭頸部扁平上皮癌の細胞株を実験系とし、高分化型の癌が浸潤癌に進行する過程で起こる核内の変化を解析した。得られた結果は、DNAメチル化・脱メチル化を中心とするクロマチン・リモデリングによって、遺伝子発現プロファイルが大きく変化し、上皮間葉転換（浸潤能獲得）が起こることを示唆した。癌の悪性転化を理解するには、個々の遺伝子の変異に加えて、ゲノムワイドなクロマチン構造の変化とそれが起こる機構を解析することが重要と思われる。