FIGURE 2.

Wnt Signalling Pathway: DKK3 binds to LRP, a WNT pathway coactivator of Frizzled, in normal mammary epithelial cells, preventing the pathway from being activated in the presence of the WNT ligand. In the absence of WNT activation, E-Cadherin binds to cytoplasmic -catenin, which is destroyed by GSK3. The DKK3 promoter, on the other hand, is hypermethylated in breast cancer, resulting in its downregulation. LRP can coactivate Frizzled in the presence of the WNT ligand in the absence of DKK3, resulting in phosphorylation of DSH, which prevents GSK3 from degrading -catenin.