Fig. 1

Canonical Wnt/β-catenin pathway: “WNT ON state”: WNT proteins, by binding to frizzled receptors and the LRP co-receptor, act to suppress the activity of glycogen synthase kinase-3β (GSK-3β). ZNRF3 promotes degradation of WNT receptor functioning as tumor suppressors. This prevents phosphorylation of downstream molecules allowing β-catenin association with Tcf/Lef in the nucleus and subsequent increased cell proliferation. “WNT OFF state”: In the absence of WNT ligand, the destruction complex of β-catenin (marked by dotted line box), a tertiary complex formed by axin, APC, CK1α and GSK 3β, will phosphorylate β-catenin, which subsequently undergoes proteasomal degradation