APC and cancer: Indeed, several publications in the mid 2000’s demonstrated that manipulation of factors up-stream of the degradation complex, at the level of the Wnt ligand and receptor, could alter the response of colorectal cancer cells even if they contained mutations to APC. For example, the promoter regions of SFRPs [79,80,81] and WIF1 [82] are hypermethylated and consequently down-regulated in the very early stages of gastrointestinal cancer, with the methylation status of certain SFRPs serving as biomarkers for cancer detection and progression [14,83].