Ubiquitin‑specific protease 7 promotes osteosarcoma cell metastasis by inducing epithelial‑mesenchymal transition

Oncol Rep. 2019 Jan;41(1):543-551. doi: 10.3892/or.2018.6835. Epub 2018 Oct 31.

Abstract

Osteosarcoma (OS) is the most common primary malignant bone tumour among adolescents and young adults; however, its molecular pathogenesis has not been completely elucidated. Ubiquitin‑specific protease 7 (USP7), a member of the deubiquitinating enzyme family, plays a role in the malignancy process of various cancer types by targeting the key oncoprotein; however, its biological function and mechanism in OS have not been elucidated. The present study demonstrated that USP7 expression in OS tumour tissues was markedly higher than that in the paired surrounding tissues, and high USP7 expression was positively correlated with the TNM stage and metastasis in patients with OS. Next, biological function assays demonstrated that USP7 knockdown markedly inhibited OS cell migration and invasion, whereas USP7 overexpression enhanced it. Notably, USP7 can directly bind with β‑catenin to activate the Wnt/β‑catenin signalling pathway and induce epithelial‑mesenchymal transition (EMT) of OS cells. Overall, USP7 overexpression could promote OS cell metastasis by activating the Wnt/β‑catenin signalling pathway by inducing EMT, suggesting that USP7 is a potential therapeutic target for OS.

MeSH terms

  • Adolescent
  • Adult
  • Bone Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Child
  • Epithelial-Mesenchymal Transition*
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Male
  • MicroRNAs / metabolism
  • Neoplasm Invasiveness / pathology
  • Neoplasm Staging
  • Osteosarcoma / pathology*
  • Protein Binding
  • Ubiquitin-Specific Peptidase 7 / genetics
  • Ubiquitin-Specific Peptidase 7 / metabolism*
  • Up-Regulation
  • Wnt Signaling Pathway
  • Young Adult
  • beta Catenin / metabolism

Substances

  • CTNNB1 protein, human
  • MicroRNAs
  • beta Catenin
  • USP7 protein, human
  • Ubiquitin-Specific Peptidase 7