Figure 2.

Common mechanisms by which the Wnt/β-catenin pathway is dysregulated in cancer. (A) Loss-of-function mutations in APC (adenomatous polyposis coli) lead to a breakdown of the destruction complex, accumulation of β-catenin in the cytoplasm, translocation of β-catenin into the nucleus, and constitutive expression of Wnt/β-catenin-dependent genes. (B) Gain-of-function mutations in β-catenin, often occurring in exon 3, prevent its N-terminal phosphorylation thus averting its ubiquitination and degradation. (C) Overexpression of FZD (frizzled) receptors or WNT ligands can lead to increased activation of the pathway. (D) Underexpression of secreted inhibitors of the pathway (i.e., secreted frizzled-related proteins, sFRPs) can also lead to increased sensitivity to Wnt ligands and increased pathway activation.