FOXO3a Is A Major Target Of Inactivation By PI3K/AKT Signaling In Aggressive Neuroblastoma

ABSTRACT: Neuroblastoma is a pediatric tumor of the peripheral sympathetic nervous system with a highly variable prognosis. Activation of the PI3K/AKT pathway in neuroblastoma is correlated with poor patient prognosis, but the precise downstream effectors mediating this effect have not been determined. Here, we identify the forkhead transcription factor FOXO3a as a key target of the PI3K/AKT pathway in neuroblastoma. FOXO3a expression was elevated in low stage neuroblastoma tumors and normal embryonal neuroblasts, but reduced in late stage neuroblastoma. Inactivation of FOXO3a by AKT was essential for neuroblastoma cell survival. Treatment of neuroblastoma cells with the dual PI3K/mTOR inhibitor PI-103 activated FOXO3a and triggered apoptosis. This effect was rescued by FOXO3a silencing. Conversely,

ORGANISM(S): Homo sapiens

SUBMITTER: Rogier Versteeg 

PROVIDER: E-GEOD-42762 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress