In this research project, we have accomplished so far as followed. First, we successfully established cell competition mouse model, in which tamoxifen administration induces RasV12 in small intestine of mice in a mosaic manner (under submission). Second, we observed apically extruded RasV12 cells in vivo and ex vivo (under submission). Third, when RasV12 was induced musically in APC-mutated epithelial cells, the number of RasV12 invading into stromal region increased. Those APC/Ras double mutated cells could expand in the villi, resulted in de novo cancer development (unpublished data). Forth, when p53 mutation was induced in non-transformed MDCK cells, the p53-mutated cells surrounded by normal cells died by necroptosis-like cell death. Furthermore p53 mutated cells generated in constitutively RasV12-expressing MDCK cells overcame the competition and survived, suggesting that Ras/p53 double mutated cells could gain the resistance against the death signal from the surrounding normal cells (unpublished data).