| Project/Area Number |
17K17573
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Experimental pathology
Tumor biology
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| Research Institution | Yamagata University (2018-2020)
Asahikawa Medical College (2017) |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 肝腫瘍 / Sleeping Beautyトランスポゾン / 肝がん / Notchシグナル / Notchシグナリング / 転移 / Myc / Ras-MAPキナーゼ経路 / 上皮間葉転換 / Notch経路 / 肝癌 / 癌 |
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| Outline of Final Research Achievements |
Liver cancer exhibits a wide spectrum of histological features, such as hepatocytic, cholangiocytic, mesenchymal, and stem/progenitor phenotypes: however, the detail of the mechanism remains unknown. In this study, I explored, using the Sleeping Beauty transposon-mediated mouse liver tumor model, the context-specific roles for the Notch signaling pathway in determining the phenotypes of liver tumors. Co-activation of the Notch pathway with the PI3 kinase pathway, MAP kinase pathway, and Myc in mouse hepatocytes induced cholangiocytic tumors, sarcomatoid hepatocellular carcinoma (HCC), and dedifferentiated HCC with lung metastasis, respectively. Of note, epithelial-mesenchymal transition (EMT) was involved in carcinogenesis of sarcomatoid HCC.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の結果、肝細胞におけるNotch経路の活性化は共に活性化するシグナルに依存したコンテクスト依存的な役割を果たすことが明らかになった。実際の肝癌において、本研究で明らかになった機序が働いている可能性が示唆され、それらシグナルを標的とした治療への発展が期待される。
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