File:Model of epigenetic and genetic abnormalities leading to early abnormal activation of the canonical Wnt pathway in the progression of colon, and other, human cancers..jpg

English: Three levels of early epigenetic events for gene silencing (red X = resulting in contributions to Wnt pathway activation) are shown. SFRP family genes, which normally help prevent Wnt proteins from interacting the their Frizzled receptors, are an example of cell membrane Wnt receptors that are frequently abnormally silenced and help lead to constitutive Wnt signaling, resulting in down regulation of the APC complex, starting at the cell membrane. This begins to decrease β-catenin degradation, resulting in increased cytoplasmic levels of this protein. While most tumors, at least among colon cancers, inactivate the APC complex through mutations in the APC gene, or through activating mutations in β-catenin, occasional tumors epigentically inactivate APC. Finally, silencing of the SOX17 gene, as per the text, results in loss of a block to TCF- β-catenin interaction helping to lead to use of the increased cellular β-catenin to activate the Wnt pathway activity. All of this concordant abnormal gene silencing primes cells for oncogenic response to key mutations, such as the APC mutations or activating mutations in β-catenin.