This idea is based on three key results: (i) The majority of human colorectal cancers harbor deletions in APC (Kinzler & Vogelstein, 1996); (ii) a dominant-negative form of TCF (dnTCF), which blocks all TCF/LEF function, inhibits the proliferation of early and advanced human colon cancer cells in vitro (van de Wetering et al, 2002); and (iii) constitutive activation of the canonical Wnt-Tcf pathway by loss of Apc induces intestinal adenomas in mice (Su et al, 1992). This evidence concerns the gene HNF4A and malignant colon neoplasm.