However, given the role of Smad4 in genomic stability (59, 60, 61) and tumor suppression (62, 63), tumorigenesis in the Smad4 KO chronic DSS mouse model is not surprising, especially in the presence of a DNA-damaging agent such as AOM (azoxymethane) (55, 56, 57). Here, SMAD4 is linked to neoplasm.