Gamma-synuclein binds to AKT and promotes cancer cell survival and proliferation

Hyperactivation of AKT plays a critical role in the survival and proliferation of cancer cells. However, the molecular mechanisms underlying AKT activation remain elusive. Here, we tested the effect of γ-synuclein, a member of the synuclein family of proteins, on the activation of AKT. We show that the expression level of γ-synuclein is increased in non-small cell lung cancer (NSCLC) tissues. γ-Synuclein binds to the protein kinase domain of AKT and promotes its phosphorylation. Overexpression of γ-synuclein in H157 cells enhances cell proliferation and protects the cells from staurosporine-induced cytotoxicity. Knockdown of γ-synuclein attenuates AKT activation and cell proliferation induced by epidermal growth factor. The effect of γ-synuclein is abolished when AKT is depleted. Thus, γ-synuclein promotes cell survival and proliferation via activating AKT and may play a causal role in the pathogenesis of NSCLC.