Schematic representation of cooperation between Wnt signaling and ITD mutations. In the presence of Wnt ligands the intracellular cascade of canonical Wnt signaling is activated via Frizzled receptors. This results in the stabilization of β-catenin protein in the cytoplasm and, thus, a higher translocation of β-catenin into the nucleus. There it forms a complex with TCF transcription factor and activates the transcription of Wnt target genes such as cyclin D1 or c-myc. In the presence of ITD mutations, β-catenin protein is stabilized independently of Wnt ligand–induced signaling. Additionally, the receptor Frizzled-4 is up-regulated. As a consequence, the canonical Wnt signaling cascade is also activated, resulting in a higher activation of β-catenin/TCF-dependent promoters and, thus, higher expression levels of Wnt target genes. EC indicates extracellular; CP, cytoplasm; and NU, nucleus.