2015 Fiscal Year Final Research Report
Functional analysis of Lgr5 in colon and ovary cancer
| Project/Area Number |
25290043
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
OKAMOTO Aikou 東京慈恵会医科大学, 医学部, 教授 (20204026)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | Lgr5 |
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| Outline of Final Research Achievements |
Lgr5 is specifically expressed in stem cells of the intestine and has an essential role in maintaining tissue homeostasis. However, the function of Lgr5 in colorectal tumourigenesis is unclear. We showed that Lgr5 is required for the tumourigenicity of colorectal cancer cells. We also showed that the transcription factor GATA6 directly enhances the expression of Lgr5. Furthermore, we demonstrated that GATA6 is upregulated in colorectal cancer cells due to the downregulation of miR-363, which directly targets GATA6. We found that Reg4, a member of the regenerating islet-derived (REG) family, is also a target of GATA6 and GATA6-mediated activation of Reg4 enhances the tumorigenicity of colon cancer cells. These results suggest that the miR-363-GATA6-LGR5/Reg4 pathway is critical for colorectal tumorigenesis.
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| Free Research Field |
分子生物学
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