Background and objective Lung cancer is the leading cancer-related death worldwide.Patients with lung cancer mainly died of tumor metastasis and invasion.Protein kinase CK2 is an ubiquitous sefine/threonine protein kinase and is frequently upregulated in various human tumors.This study aims to explore the effect and molecular mechanism of the invasion and migration of lung adenocarcinoma A549 cells after knock-down of CK2α expression.Methods The pSilencerTM 4.1-siCK2α-eGFP oflentiviral-me-diated shRNA was constructed.The expression of CK2α was knock-downed,and a stable A549 cell line was established.The invasion and migration ofA549 cell line was detected through Transwell and Boyden chamber assays.The protein expression of the PI3K/Akt signaling pathway and mesenchymal-to-epithelial transition (EMT) was evaluated using Westem blot analysis.Results The invasion and migration of A549 cells were significantly inhibited after the knockdown of CK2α expression compared with that in the control group,p-PTEN,Akt,p-Akt473,p-Akt308,p-PDK1,p-c-Raf,and p-GSK-3β were significantly downregnlated,whereas PTEN was upregulated.Moreover,vimentin,β-catenin,Snail,MMP2,and MMP9 were significantly downregnlated after reducing the CK2α expression.Conclusion CK2α might regulate the invasion and migration of A549 cells through the PI3K/Akt/GSK-3β/Snail signaling pathway,which controls EMT in lung adenocarcinoma.