2019 Fiscal Year Final Research Report
Regulation of Features of Liver Cancer Stem-like Cells through the TCF-4/CLAUDIN-2/HES1 Axis
| Project/Area Number |
17K09445
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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 |
Gastroenterology
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| Research Institution | Kurume University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | T-cell factor-4 / Wnt / Claudin-2 / Hes1 |
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| Outline of Final Research Achievements |
We investigated the Wnt-Notch crosstalk in liver cancer cells. Loss of SxxSS motif in TCF-4 led to upregulation of CLAUDIN-2 (CLDN2) mRNA. This finding coupled with upregulation of HES1 was also reproduced at protein levels in both sphere-forming J cells, that do not have SxxSS, and K-mutant cells, having engineered SxxSA motif. These findings suggested HES1 expression was regulated by the critical transcription factor TCF-4 isoforms in liver cancer cells.
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| Free Research Field |
消化器病学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では，独自のTCF-4 isoformを用いWnt-Notch crosstalkの解明にアプローチする点が最大の特色であった．Cancer sphereに濃縮されるCLAUDIN-2はleaky tight junctionを形成し，かつNotchシグナル活性化を促進しHES1発現を増強することで癌幹細胞のstemness維持に寄与していると考えている．意義としては，Wnt/TCF-4下流分子CLAUDIN-2からのNotchシグナルリレーが明らかになり，CSCに対する新規治療標的を探索できる可能性を増やすことができる点だと考えている．
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