Initially, to test if the expression of PHLDA1/2 required hyperactivated ERK signaling, we treated HEK293 cells with the tumor promoter TPA or with EGF, which elicits strong and prolonged, or moderate and transient ERK activity, respectively, or with insulin, which preferentially induces AKT activity (Fig. 7a). Here, PHLDA1 is linked to neoplasm.