Mutations in the APC (adenomatous polyposis coli) gene occur in most sporadic colorectal cancers. But although APC loss is important in tumour initiation, it is unclear whether tumours form in the epithelial stem cells of the intestinal crypts or in the differentiated cells of the villus. On p. 1443, Andreu and colleagues report that Apc loss in the mouse intestine rapidly induces crypt-restricted premalignant changes. Using a conditional gene-ablation approach, they examined the effects of Apc loss along the crypt-villus axis of the mouse small intestine. Apc loss activates β-catenin signalling in both compartments but only the crypt cells respond with increased proliferation and apoptosis, and impaired cell migration. The activation of β-catenin signalling also alters crypt cell fate, promoting their commitment to the Paneth cell lineage. Overall, these results indicate that tumorigenesis caused by the loss of Apc in the colon occurs among the stem cells in the...

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