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Biochem Cell Biol. 2018 Dec 3:1-8. doi: 10.1139/bcb-2018-0236. [Epub ahead of print]

Carboxypeptidase E-ΔN promotes migration, invasiveness, and epithelial-mesenchymal transition of human osteosarcoma cells via the Wnt-β-catenin pathway.

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a Department of Geriatrics, The First Affiliated Hospital of China Medical University, Shenyang 110001, P. R. China.
b Department of Orthopedic Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, P. R. China.


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-ΔN, is implicated in tumor metastasis and poor prognosis. In this study, we investigated the effect of CPE-ΔN on cell migration, invasiveness, and the 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 cell migration and invasiveness, and promoted the EMT process. Further, overexpression of CPE-ΔN increased the levels of c-myc and nuclear β-catenin in OS cells, which suggested the CPE-ΔN promotes activation of the Wnt-β-catenin pathway in OS cells. Treatment with β-catenin small interfering RNA (siRNA) inhibited the migration and invasiveness of CPE-ΔN-overexpressing cells, and reduced the expression of E-cadherin. Together, these results suggest that CPE-ΔN promotes migration, invasiveness, and the EMT of OS cells via the Wnt-β-catenin signaling pathway.


carboxypeptidase E; epithelial–mesenchymal transition; metastasis; métastase; osteosarcoma; ostéosarcome; transition épithélio-mésenchymateuse; β-catenin; β-caténine


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