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.
Biochem Cell Biol. 2019 Aug;97(4):446-453. doi: 10.1139/bcb-2018-0236. Epub 2018 Dec 3.
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.
骨肉瘤（OS）是儿童和青少年中最常见的恶性骨肿瘤，转移性 OS 是 OS 相关死亡的主要原因。羧肽酶 E（CPE）已知在某些癌症类型中高度表达，其 N 端截断形式 CPE-ΔN 与肿瘤转移和预后不良有关。在这项研究中，我们研究了 CPE-ΔN 对 OS 细胞迁移、侵袭和上皮-间充质转化（EMT）的影响，并阐明了其分子机制。我们首先构建了 CPE-ΔN 过表达的人骨肉瘤细胞系（143B 和 U2OS 细胞），发现 OS 细胞中 CPE-ΔN 的异位表达增强了细胞迁移和侵袭，并促进了 EMT 过程。此外，CPE-ΔN 的过表达增加了 OS 细胞中 c-myc 和核 β-连环蛋白的水平，这表明 CPE-ΔN 促进了 OS 细胞中 Wnt-β-连环蛋白信号通路的激活。β-连环蛋白小干扰 RNA（siRNA）的处理抑制了 CPE-ΔN 过表达细胞的迁移和侵袭，并降低了 E-钙粘蛋白的表达。综上所述，这些结果表明 CPE-ΔN 通过 Wnt-β-连环蛋白信号通路促进 OS 细胞的迁移、侵袭和 EMT。
