APC and neoplasm: In contrast to tumorigenesis initiated by dedifferentiation (tumor generated from intestinal epithelial cell of villin-creERT2/APC lox/lox/K-rasG12D/+ mice) [4], where tumor cells were Lgr5− and generated independently of R-spondin 1, tumor cells in the current study were Lgr5+ and generated dependently on R-spondin 1 (Figure 6), suggesting that tumor cells generated by DMBA treatment and PP2A deficiency in mouse Lgr5+ cells were indeed intestinal CSCs and could serve as surrogates of human colorectal CSCs [34].