The role of ZBTB38 in promoting migration and invasive growth of bladder cancer cells

Oncol Rep. 2019 Mar;41(3):1980-1990. doi: 10.3892/or.2018.6937. Epub 2018 Dec 18.

Abstract

Bladder cancer is the most common malignancy of the urinary tract, and ~50% of patients with bladder cancer experience recurrence and metastasis. The results of mass spectrometry revealed that the expression of zinc finger and BTB domain‑containing 38 (ZBTB38) was higher in highly aggressive human bladder cancer 253J B‑V cells compared with in the less aggressive bladder cancer 253J cells. However, the association between ZBTB38 and bladder cancer is currently not well defined, and the association of ZBTB38 with migration and invasive growth of bladder cancer cells remains unclear. Previous studies have suggested that ZBTB38 may act as an oncogene, similar to Kaiso. Furthermore, analysis of a clinical database suggested that ZBTB38 expression may be associated with poor prognosis of patients with bladder cancer. Using cell proliferation, migration and invasion assays, and western blotting, the present study demonstrated that ZBTB38 promoted the migration and invasive growth of bladder cancer cells, but inhibited their proliferation. Further experiments suggested that ZBTB38 promoted epithelial‑mesenchymal transition and the expression levels of genes downstream of the Wnt/β‑catenin signaling pathway. Notably, further experiments using a xenograft tumor metastasis model revealed that ZBTB38 promoted bladder cancer lung metastasis in vivo. These findings suggested that ZBTB38 promoted migration and invasive growth of bladder cancer cells through facilitation of the Wnt/β‑catenin signaling pathway. To the best of our knowledge, this is the first study to reveal that ZBTB38 may promote migration and invasive growth of bladder cancer cells via modulation of the Wnt/β‑catenin signaling pathway.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation
  • Disease-Free Survival
  • Epithelial-Mesenchymal Transition
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung / pathology
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / secondary
  • Male
  • Mice
  • Mice, SCID
  • Neoplasm Invasiveness / pathology
  • Neoplasm Recurrence, Local
  • RNA, Small Interfering / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Survival Analysis
  • Urinary Bladder / pathology
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / pathology*
  • Wnt Signaling Pathway*
  • Xenograft Model Antitumor Assays

Substances

  • RNA, Small Interfering
  • Repressor Proteins
  • ZBTB38 protein, human