The Mechanism of disintegration and redifferentiation of cell adhesion proteins through CDX2 in chemotherapy refractory colorectal cancer.

Research Project

Project/Area Number	25460962
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Gastroenterology
Research Institution	Keio University
Principal Investigator	FUNAKOSHI SHINSUKE 慶應義塾大学, 医学部, 講師 (20297352)
Research Collaborator	LYNCH JOHN P University of Pennsylvania, Department of Medicine, Division of Gastroenterology, Associate Professor of Medicine AZUMA TOSHIFUMI 東京歯科大学, 歯学部, 教授 (00222612)
Project Period (FY)	2013-04-01 – 2016-03-31
Project Status	Completed (Fiscal Year 2015)
Budget Amount *help	¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000) Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords	CDX2 / SP細胞 / 細胞接着関連タンパクの破綻 / 化学療法抵抗性大腸癌 / 大腸癌 / Cdx2 / C－MET / 細胞接着 / columnar morphogenesis / ShRNA / IGF / c-Met / SiRNA
Outline of Final Research Achievements	Generating pHT- control, pHT-Cdx2, and pHT-Cdx2-ShRNA-infected Colon cancer cells, the phosphorylation states of several receptor tyrosine kinases and the expression of cell adhesion marker were analyzed. Side population cells derived from each cancer cells were investigated in terms of cell function, proliferation, adhesion and invasion potential. Using spheroid-based drug screen, we are determined to pursue the mechanism of disintegration and redifferentiation of cell adhesion proteins through CDX2 in chemotherapy refractory colorectal cancer. Especially, we focus on the mechanism the regulation of Rac1 expression by Cdx2.