2015 Fiscal Year Final Research Report
Analysis of the roles of linear polyubiquitin chains and Sharpin in hepatocellular carcinoma
| Project/Area Number |
25460981
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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 | The University of Tokyo |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Yasuo 東京大学, 医学部附属病院, 助教 (40422290)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | 肝臓 / 肝細胞癌 / Sharpin / 癌関連遺伝子 / 浸潤能 |
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| Outline of Final Research Achievements |
Sharpin is one of the components of the LUBAC, which specifically generates linear polyubiquitin chains to activate NF-kB pathway. Sharpin is also reported to be up-regulated in various types of cancers including HCC and implicated in cancer progression. In this study, we showed that Sharpin transcription was up-regulated in HCC tissues, and significantly correlated with tumor size and histology. Increased expression of Sharpin enhanced the invasion of hepatoma cells, and cDNA microarray analysis identified that Versican, an extracellular matrix proteoglycan, was also up-regulated in Sharpin expressing cells. Knocking down of Versican greatly attenuated the invasion of hepatoma. Furthermore, Sharpin overexpression resulted in activation of Versican promoter activity. Taken together, these results suggest that Sharpin plays crucial roles in tumor-invasiveness during cancer progression through transactivating Versican.
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| Free Research Field |
肝臓病学
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