Carboxypeptidase E-Delta N promotes migration, invasiveness, and epithelial-mesenchymal transition of human osteosarcoma cells via the Wnt-beta-catenin pathway

摘要

Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents, and metastatic OS is the major cause of OS-related death. Carboxypeptidase E (CPE) is known to be highly expressed in some cancer types, and its N-terminal truncated form, CPE-Delta N, is implicated in tumor metastasis and poor prognosis. In this study, we investigated the effect of CPE-Delta N on cell migration, invasiveness, and the epithelial-mesenchymal transition (EMT) of OS cells, and illustrated the molecular mechanisms. We first constructed CPE-Delta N overexpressing human OS cell lines (143B and U2OS cells), and found that ectopic CPE-Delta N expression in OS cells enhanced cell migration and invasiveness, and promoted the EMT process. Further, overexpression of CPE-Delta N increased the levels of c-myc and nuclear beta-catenin in OS cells, which suggested the CPE-Delta N promotes activation of the Wnt-beta-catenin pathway in OS cells. Treatment with beta-catenin small interfering RNA (siRNA) inhibited the migration and invasiveness of CPE-Delta N-overexpressing cells, and reduced the expression of E-cadherin. Together, these results suggest that CPE-Delta N promotes migration, invasiveness, and the EMT of OS cells via the Wnt-beta-catenin signaling pathway.