β-catenin confers resistance to PI3K and AKT inhibitors and subverts FOXO3a to promote metastasis in colon cancer

The crosstalk between the transcriptional activity of β-catenin and FOXO3a reveals unexpected pro-metastatic cooperative effects of these pathways through concurrent modulation of cell adhesion and motility programs. In tumors with high FOXO3a and β-catenin activity, the proapoptotic effect of FOXO3a is subverted and the pro-proliferative effect of β-catenin is also dampened, but pro-metastatic pathways are activated. These findings suggest that caution should be exerted when using targeted inhibitors that activate FOXO3a in tumors with high β-catenin activity, as coactivation of both pathways also correlates with more aggressive disease in humans.