ISG15 and lung cancer: Consistent with this finding was evidence that the DUB USP4 promoted epithelial–mesenchymal transition (EMT) by stabilizing the PRL-3 expression.50 USP18 enzymatically removes ISG15 from complexed proteins.51 USP18 was previously found to play an oncogenic role in the survival and growth of lung cancer cells.17–19,21,22 It was also shown that USP18 enhanced EMT by stabilizing Twist1 expression in glioblastoma.23 The present work found that USP18 knock-down reduced 14-3-3ζ expression and inhibited lung cancer metastasis.