The role of epigenetic reprogramming for the acquisition of pluripotency in head and neck cancer stem cells
| Project/Area Number |
16K11255
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | National Hospital Organization, Kyushu Cancer Center |
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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)
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| Research Collaborator |
NIKAIDO ITOSHI
TO SATOSHI
WAKASAKI TAKAHIRO
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | epigenetics / YAP1 / stemness / carccinogenesis model / mouse / 頭頸部癌 / 発癌モデル / マウス発癌 / epigenetic / マウス発がんモデル / YAP / 多分化能 / 幹細胞 / エピジェネティク |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(16 results)
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[Journal Article] Treatment of Squamous Cell Carcinoma of the Esophagaus Synchronously Associated with Head and Neck Cancer2017
Author(s)
Morita M,Egashira A,Nakai Y,Kagawa M，Sugiyama M,Yoshida D,Ota M,Ikebe M,Masuda M,Inoue Y,Kunitake N,Toh Y
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Journal Title
in vino
Volume: 31
Pages: 909-916
Related Report
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[Presentation] Transcriptional addiction to YAP1 -the major driving force of oral cancer carcinogenesis and evolution ?-2019
Author(s)
Muneyuki Masuda, Hirofumi Omori, Kuniaki Sato, Kenichi Taguchi, Masashige Bando, Satoshi Toh, Katsuhiko Shirahige, Koshi Mimori, Akira Suzuki
Organizer
AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research
Related Report
Int'l Joint Research
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[Presentation] Transcriptional addiction to YAP1 -the major driving force of oral cancer carcinogenesis and evolution ?-2019
Author(s)
Muneyuki Masuda, Hirofumi Omori, Kuniaki Sato, Kenichi Taguchi, Masashige Bando, Satoshi Toh, Katsuhiko Shirahige, Koshi Mimori, Akira Suzuki
Organizer
The Hippo Pathway: Signaling, Cancer, and Beyond
Related Report
Int'l Joint Research
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