Search for novel Lgr5 ligands and receptor of Reg4

Research Project

Project/Area Number	17K19584
Research Category	Grant-in-Aid for Challenging Research (Exploratory)
Allocation Type	Multi-year Fund
Research Field	Tumor biology and related fields
Research Institution	The University of Tokyo
Principal Investigator	Kawasaki Yoshihiro 東京大学, 定量生命科学研究所, 特任准教授 (10376642)
Project Period (FY)	2017-06-30 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000) Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000) Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords	Lgr5 / Reg4
Outline of Final Research Achievements	We have found that cooperation between Lgr5 and Reg4 is important for the tumorigenicity of colon cancer cells. It has been shown that LGR5 is an R-spondins receptor. However, we have obtained some preliminary data showing the existence of novel ligands for Lgr5. In this research project, we created a system that could purify Lgr5 and Reg4 binding proteins from cell culture medium and cell lysates by affinity chromatography.
Academic Significance and Societal Importance of the Research Achievements	これまで、疾患発症におけるLgr5の役割や重要性は十分に明らかにされていなかった。そのため、Lgr5やその関連因子を標的とした治療法や診断法の開発は進んでいない。今後、本研究によって得られた知見を基にして新規Lgr5リガンドを同定することができれば、Lgr5関連シグナル経路の異常による癌発症メカニズムが明らかになるだけでなく、これまでに類を見ない分子標的治療法の開発にも繋がる可能性があると考える。