2011 Fiscal Year Final Research Report

Analysis of the molecular mechanisms by which CDX2 supresses colon caner cell proliferation

Research Project

Project/Area Number	22790380
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Single-year Grants
Research Field	Experimental pathology
Research Institution	Kyoto University
Principal Investigator	AOKI Koji 京都大学, 医学研究科, 助教 (40402862)
Project Period (FY)	2010 – 2011
Keywords	CDX2 / 細胞増殖 / 大腸癌 / 癌抑制遺伝子 / 転写
Research Abstract	CDX2 is a homebox transcription factor that is expressed specifically in the intestinal epithelial cells. We have previously shown that CDX2 supresses colonic tumorigensis, using a knockout mouse model. In this study, we have found that CDX2 suppresses proliferation of colon cancer cells through its non-transcriptional function, wheares it acts as a transcription factor. The block of cell proliferation caused by CDX2 is mediated partilly through increased level of p27 protein, a CDK inhibitor. In addition, we have found ubiqutin E1-like enzyme ATG7 as a protein interacting with CDX2, and that CDX2 stimulates autophagy. Interestingly, CDX2 induces a kind of cell death through autophagy. Thease results have suggested that CDX2 suppresses colonic tumorigensis through ATG7-mediated stimulation of autophagy.