The role of epigenetic reprogramming for the acquisition of pluripotency in head and neck cancer stem cells

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K11255
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: National Hospital Organization, Kyushu Cancer Center
• Principal Investigator: Masuda Muneyuki 独立行政法人国立病院機構(九州がんセンター臨床研究センター), その他部局等, 頭頸科部長 (90284504)
• Research Collaborator: NIKAIDO ITOSHI ; TO SATOSHI ; WAKASAKI TAKAHIRO
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: epigenetics / YAP1 / stemness / carccinogenesis model / mouse

Outline of Final Research Achievements

1.We have developed an ultra-rapid (within 2 weeks) epigenetic mouse carcinogenesis model by the conditional activation of the transcription coactivator YAP1 in the mouse oral epithelium. We also found that YAP1 activation is a strong driver of head and neck squamous cell carcinoma (HNSCC) in both onset and evolution settings through the investigations on human HNSCC tumor samples and cell lines. The more precise epigenetic mechanism is under evaluation. Parts of these results were presented in the symposium of Japan Cancer Association Annual meeting 2019 and are now under review in an English journal.
2. It was also found that YAP1 and SOX2 cooperatively activate transcription of a set of genes and thereby facilitate induction and maintenance of HNSCC stemness. These results are under review in an English journal.

Free Research Field

頭頸部癌

Academic Significance and Societal Importance of the Research Achievements

我々の結果は、現在の遺伝子変異を対象としたprecision medicineの恩恵を受けていない頭頸部癌に対してYAP1を標的としたepigeneticな分子標的治療の可能性を示唆するものであり、頭頸部癌治療に新たな活路を開く可能性がある。また、頭頸部癌（口腔）epigenetic発がんマウスモデルは頭頸部癌研究のみならず、世界的に注目を集めているYAP1阻害剤の開発プラットフォームとして極めて有用と考えられる。