APP significantly impacts IGF-1-mediated activation of AKT and its downstream effectors. Both MDA-MB-231 control (shluc) and APP-kd (shAPP) cells were treated with EGF (50 ng/ml), LPS (100 ng/ml), or IGF-1 (100 ng/ml) as indicated. (A) EGF-mediated Erk activation was assessed in the APP knock-down cells post stimulation with EGF. (B) LPS-mediated activation of pro-inflammatory response in the APP knockdown cells was tested by demonstrating the level of IκBα expression and NF-κB activation (phosphorylated p65 at S536). (C) IGF-1-stimulated Akt activation and phosphorylation of Akt target proteins such as GSK3β (S9) and FOXO1 (T24) were examined. (D) APP affects the expression of β-Catenin, a target of GSK3β, and its downstream targets such as Survivin and CD44, but not Cyclin D1.