In this work, we have demonstrated that serum deprivation induced a rapid and prolonged phosphorylation of Akt that was drastically prevented by EGFR inhibition, suggesting that serum withdrawal-dependent activation of EGFR is required to trigger PI3K/Akt signaling cascade and, consequently, to induce Sp1-dependent upregulation of P2X7R in neuroblastoma cells. The gene discussed is SP1; the disease is neuroblastoma.