Carboxypeptidase E-ΔN promotes migration, invasion and epithelial-mesenchymal transition of human osteosarcoma cell lines through the Wnt/β-catenin pathway.

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 demonstrated to be highly expressed in some cancer types, and its N-terminal truncated form, CPE-ΔN, is implicated in tumor metastasis and poor prognosis. In this study, we investigated the effect of CPE-ΔN on cell migration, invasion and epithelial-mesenchymal transition (EMT) of OS cells, and illustrated the molecular mechanisms. We first constructed CPE-ΔN overexpressing human OS cell lines (143B and U2OS cells), and found that ectopic CPE-ΔN expression in OS cells enhanced cellular migratory and invasiveness abilities, and promoted EMT process. Further, overexpression of CPE-ΔN increased c-myc and nuclear β-catenin levels in OS cells, which suggested CPE-ΔN promoted the activation of Wnt/β-catenin pathway in OS cells. Treatment with β-catenin small interfering RNA (siRNA) inhibited the migratory and invasive abilities of CPE-ΔN-overexpressing cells, and reversed E-cadherin expression. Together, these results suggest that CPE-ΔN promotes migration, invasion and EMT of OS cells via the Wnt/β-catenin signaling.