Importantly, VilCreER;Apcfl/+;KrasG12D/+;Alk5CA tumours exhibited high expression of the Alk5CA transgene and prominent p-SMAD3 staining (Fig. 4d, e and Supplementary Fig. 4a), in contrast to APC-deficient tumours lacking Kras mutation (Supplementary Fig. 3h, j). This evidence concerns the gene SMAD3 and neoplasm.