DEAD-Box Helicase 3 X-Linked Promotes Metastasis by Inducing Epithelial-Mesenchymal Transition via p62/Sequestosome-1.

Abstract

DEAD-Box Helicase 3 X-Linked (DDX3X) is a member of the DEAD-box helicases that play a crucial role in RNA metabolism. Although DDX3X has been shown to contribute to tumorigenesis, the detailed mechanisms by which DDX3X functions in pancreatic ductal adenocarcinoma (PDAC) biogenesis remain poorly understood. The goal of the present study was to elucidate the molecular mechanisms by which DDX3X contributes to tumorigenesis in PDAC. Kaplan-Meier curves, the log-rank test, t test and Cox regression were used to analyze the relationship between DDX3X expression and the clinicopathological features of PDAC patients. DDX3X and p62 expression in human PDAC tissues was analyzed by immunohistochemistry. Monolayer scratch healing assays, cell migration assays and nude mouse lung metastasis models were used to evaluate the effect of DDX3X on metastasis in vitro and in vivo. Western blot analysis was used to assess the expression of proteins in the signaling pathway. We authenticated high DDX3X expression was associated with a poor prognosis in PDAC. The loss of DDX3X attenuated the migratory capacity of PDAC cells in vitro and in vivo. DDX3X was shown to facilitate epithelial-mesenchymal transition (EMT) and the phosphorylation of p65 and eIF2α. Moreover, DDX3X displayed oncogenic activity by promoting p62 accumulation. Our results demonstrated that DDX3X activates NF-κB and promotes metastasis by inducing EMT via p62.