Oncogenic Function of DACT1 in Colon Cancer through the Regulation of β-catenin
Figure 10
Putative model of how DACT1 mediates the activation of β-catenin signaling in colon cancer cells.
Left: In unstimulated normal colon cells lacking DACT1, the axin/GSK-3β/APC phosphorylate β-catenin and target it for ubiquitin-mediated degradation. Right: In colon cancer cells that express high levels of DACT1, DACT1 binds to β-catenin. DACT1 then binds and inhibits GSK-3β, which inhibits the function of the destruction complex, resulting in the release of β-catenin. This leads to increased nuclear and cytoplasmic fractions of β-catenin, and increased levels of membrane-bound β-catenin. Subsequently, the migration and invasion capacities of the colon cancer cells are enhanced and downstream target genes are activated.