The role of SOX18 in bladder cancer and its underlying mechanism in mediating cellular functions

Life Sci. 2019 Sep 1:232:116614. doi: 10.1016/j.lfs.2019.116614. Epub 2019 Jun 28.

Abstract

Aims: SRY-box 18 (SOX18) is a transcription factor known for its role in regulating cell differentiation and lymphatic and blood vessel development. It has been reported that SOX18 was involved in various diseases, including cancer. This study aimed to explore the significance and biological function of SOX18 in bladder cancer (BCa).

Materials and methods: SOX18 expression in BCa and normal tissues was analyzed by immunohistochemistry, and SOX18 expression in BCa cell lines was quantified by western blotting and quantitative real-time PCR. The role of SOX18 on the proliferation, migration and invasion of BCa cells was explored by CCK-8 and transwell invasion assays in vitro. Cell cycle was measured by flow cytometry assays. Western blotting and qRT-PCR were performed to investigate the potential mechanisms by which SOX18 leads to tumor progression.

Key findings: SOX18 was significantly upregulated in BCa and its expression was associated with clinical features of patients with BCa. Our data demonstrated that SOX18 promoted cell proliferation via accelerating cell cycle and by regulating c-Myc and Cyclin D1, promoted cell invasion via upregulation of MMP-7. Moreover, phosphorylation of c-Met and Akt regulated by SOX18 was identified to be involved in the process of cell migration and invasion, indicating the vital role of SOX18 in the metastasis of BCa.

Significance: Our data demonstrated a cancer-promoting effect of SOX18 in BCa, revealed the potential mechanisms of SOX18 in mediating cellular functions, and indicated that SOX18 may serve as a promising progression and prognostic biomarker and a therapeutic target for BCa.

Keywords: Bladder cancer; Cell cycle; Cell invasion; MMPs; SOX18.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Animals
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Cyclin D1 / metabolism
  • Female
  • G1 Phase / physiology
  • Heterografts
  • Humans
  • Male
  • Matrix Metalloproteinase 7 / metabolism
  • Mice
  • Mice, Nude
  • Middle Aged
  • Neoplasm Invasiveness
  • Proto-Oncogene Proteins c-myc / metabolism
  • S Phase / physiology
  • SOXF Transcription Factors / biosynthesis
  • SOXF Transcription Factors / genetics
  • SOXF Transcription Factors / metabolism*
  • Transcriptome / genetics
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / pathology

Substances

  • CCND1 protein, human
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • SOX18 protein, human
  • SOXF Transcription Factors
  • Cyclin D1
  • MMP7 protein, human
  • Matrix Metalloproteinase 7