The TGFβ pathway has been previously reported to form a gradient along the vertical axis of the intestinal epithelium with the highest activity in differentiated cells and lowest activity in the crypt.21 However, studies that have genetically ablated TGFβ signalling either via receptor or SMAD4 deletion, have not reported marked effects on homeostasis.22, 23 For our studies if tumour cells arise further up the crypt–villus axis, they may be exposed to a high level of TGFβ signalling that might prevent dedifferentiation and limit proliferation. Here, SMAD4 is linked to neoplasm.