Given the inhibition results of KY1022 on API-2-induced cell motility and overcoming the effects of KY1022 on API-2-induced resistance to apoptosis, our study suggests that the combination treatment targeting the Wnt/β-catenin pathway with the AKT inhibitors is a promising therapeutic approach to improve the clinical efficiency of treating CRC patients harboring an APC mutation. Here, APC is linked to colorectal carcinoma.