Notably, while ectopic expression of either p110αH1047R, p110αE542K, or p110αE545K, all of which are constitutive activation mutants of p110α associated with breast cancer [12,40,41], let to activation of AKT and ERK, it significantly increased the expression of FBXO3, accompanied with the up-regulated USP4, Twist1, and β-catenin protein expression (Figs 5B, S4B, and S4C). Here, USP4 is linked to breast cancer.