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2015 Fiscal Year Final Research Report

Functional analysis of Lgr5 in colon and ovary cancer

Research Project

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Project/Area Number 25290043
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Tumor biology
Research InstitutionThe University of Tokyo

Principal Investigator

Kawasaki Yoshihiro  東京大学, 分子細胞生物学研究所, 准教授 (10376642)

Co-Investigator(Kenkyū-buntansha) OKAMOTO Aikou  東京慈恵会医科大学, 医学部, 教授 (20204026)
Project Period (FY) 2013-04-01 – 2016-03-31
KeywordsLgr5
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.

Free Research Field

分子生物学

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Published: 2017-05-10  

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