Overall, our study suggests the existence of a transcriptional regulatory circuit that is perturbed in human cancer and which begins with the germline overexpression of c-MYC, causing down-regulation of KLF6 which then reduces the transactivation of CDH1, which in turns feeds c-MYC expression through β-catenin and LEF/TCF transcriptional complex activation. Here, HNF4A is linked to cancer.