Phosphorylation of AEG-1 suppresses NF-κB signaling in gastric cancer.

Astrocyte elevated gene-1 (AEG-1) is oncogenic in gastric cancer; however, its underlying mechanism has not been fully elucidated. In this study, we identified serine 308 (Ser308) as a phosphorylation site of AEG-1 in gastric cancer cells. By constructing AEG-1 point mutants to overexpress phospho-mimetic AEG-1 (S308D, serine-to-aspartate) and dephospho-mimetic AEG-1 (S308A, serine-to-alanine), we found that phosphorylation of AEG-1 at Ser308 significantly suppressed cell growth and migration, accompanied by downregulation of p65 NF-κB-mediated transcription of the downstream target genes FOS and IL-8. Mechanistically, TNF-α-induced dephosphorylation of AEG-1 at Ser308 promoted p65 NF-κB nuclear accumulation and activation through protein-protein interaction. This study reveals a novel phosphorylation-dependent switch that regulates AEG-1-mediated NF-κB signaling in gastric cancer.