Figure 1

Simplified diagram of the canonical Wnt/β-catenin signaling pathway. Wnt proteins bind to receptors thought to be composed of a Frizzled protein and either of the low density lipoprotein receptor-related proteins LRP5 or LRP6. Signaling via Dishevelled and/or Axin then results in inactivation of a multiprotein complex that normally renders β-catenin unstable. This complex (shown by a dotted rectangle) includes Axin, APC, and glycogen synthase kinase-3β (GSK-3β). By inhibiting this complex, Wnt signals lead to accumulation of β-catenin in the cytosol and its entry into the nucleus. Once in the nucleus, β-catenin binds to proteins of the T-cell factor (Tcf)/lymphoid enhancer factor-1 (Lef1) family and modulates the expression of several target genes. ^* Components of the pathway identified as oncogenes in naturally occurring mouse or human cancers, ^** components identified as tumor suppressors.