Death‐associated protein kinase 1 suppresses hepatocellular carcinoma cell migration and invasion by upregulation of DEAD‐box helicase 20

Abstract

Death associated Protein Kinase 1(DAPK) is a calcium/calmodulin kinase playing a vital role as a suppressor gene in various cancers. Yet its role and target gene independent of p53 is still unknown in Hepatocellular Carcinoma Cell (HCC). In this study, we discovered that DAPK suppressed HCC cell migration and invasion instead of proliferation or colony formation. Using proteomics approach, we identified DEAD‐Box Helicase 20(DDX20) as an important downstream target of DAPK in HCC cells and was critical for DAPK‐mediated inhibition of HCC cell migration and invasion. Using integrin inhibitor RGD and GTPase activity assays, we discovered that DDX20 suppressed HCC cell migration and invasion via CDC42‐integrin pathway, which was reported as an important downstream pathway of DAPK in cancer before. Further research using cycloheximide found that DAPK attenuates the proteasomal degradation of DDX20 protein, which is dependent on the kinase activity of DAPK. Our results shed light on new functions and regulation for both DAPK and DDX20 in carcinogenesis and provides new potential therapeutic targets for HCC.