In this study, we show that NatD-mediated N-α-terminal acetylation ofhistone H4 promotes lung cell invasion through antagonizing serine phosphorylationof histone H4 by CK2α The results demonstrate a critical interplay betweentranscriptional and epigenetic control during lung cancer progression associatedwith EMT of cancer cells, thus suggesting that NatD could be a potential therapeutictarget for lung cancer. Here, NAA40 is linked to lung cancer.