SOX10 is over-expressed in bladder cancer and contributes to the malignant bladder cancer cell behaviors

Clin Transl Oncol. 2017 Aug;19(8):1035-1044. doi: 10.1007/s12094-017-1641-2. Epub 2017 Mar 3.

Abstract

Purpose: To detect the expression level and significance of SOX10 in human bladder cancer.

Methods: Immunohistochemical analyses were performed to assess SOX10 protein level using a bladder cancer tissue microarray (including 59 spots of cancer tissues and 46 spots of paired normal tissues) and 31 specimens and to define the relationship between SOX10 and clinicopathological bladder cancer characteristics in patients. SOX10 protein and mRNA levels in bladder cancer cell lines (T24, 5637, BIU87, EJ) and transitional cell papilloma cell line (RT4) were tested by western blotting and quantitative real-time PCR (q-PCR), respectively. Cell Counting Kit-8 (CCK-8) and colony formation assays were performed to investigate bladder cancer cell proliferation after SOX10 knockdown. The effect of SOX10 on cell migration and invasion was analyzed by Transwell and Matrigel assays. Kaplan-Meier survival curves and Cox regression analyses were used to evaluate SOX10 prognostic significance for bladder cancer patients. The mechanisms by which SOX10 promote bladder cancer progression were examined by western blotting.

Results: SOX10 protein was upregulated in 74.4% of bladder cancer tissues compared with adjacent normal tissues (32.6%). SOX10 protein was also upregulated in malignant cell lines. In addition, high SOX10 expression was related with clinical stage (P = 0.008), T stage (P = 0.004), histological grade (P = 0.002) and lymph node metastasis (P = 0.006). Kaplan-Meier survival curves and Cox regression analyses showed that SOX10 functioned as an independent prognostic factor for overall survival. SOX10 knockdown in bladder cancer cells significantly impacted proliferation, migration and invasion, and SOX10 might promote bladder cancer progression by altering β-catenin and Met expression.

Conclusion: SOX10 was over-expressed in bladder cancer and promoted malignant bladder cancer cell behaviors. SOX10 has potential as a molecular target for bladder cancer treatment.

Keywords: Bladder cancer; Cell proliferation; Invasion; SOX10; Therapeutic target.

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Transitional Cell / genetics
  • Carcinoma, Transitional Cell / metabolism
  • Carcinoma, Transitional Cell / secondary*
  • Case-Control Studies
  • Cell Movement
  • Cell Proliferation
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lymphatic Metastasis
  • Male
  • Prognosis
  • SOXE Transcription Factors / genetics
  • SOXE Transcription Factors / metabolism*
  • Survival Rate
  • Tumor Cells, Cultured
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology*

Substances

  • Biomarkers, Tumor
  • SOX10 protein, human
  • SOXE Transcription Factors