SOX2 Is a Marker for Stem-like Tumor Cells in Bladder Cancer

Stem Cell Reports. 2017 Aug 8;9(2):429-437. doi: 10.1016/j.stemcr.2017.07.004.

Abstract

It has been reported that functionally distinct cancer stem cells (CSCs) exist in human bladder cancer (BCa). Here, we found that Sox2, a transcription factor that is well characterized as a marker for stem cells, is upregulated in both mouse and human BCa. Sox2 expression is absent in normal urothelial cells, but it begins to be expressed in pre-neoplastic bladder tumors and continues to be expressed in invasive mouse BCa. Using s as a reporter of Sox2 transcriptional expression, we demonstrated that Sox2-expressing cells mark a subpopulation of tumor cells that fuel the growth of established BCa. SOX2-positive cells also expressed other previously reported BCa CSC markers, including Keratin14 (KRT14) and CD44v6. Ablation of Sox2-expressing cells within primary invasive BCa led to enhanced tumor regression, supporting the essential role of SOX2-positive cells in regulating BCa maintenance and progression. Our data show that Sox2 is a marker of bladder CSCs and indicate it as a potential clinical target for BCa therapy.

Keywords: Sox2; bladder cancer; cancer stem cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor*
  • Cell Line, Tumor
  • Cell Lineage / genetics
  • Cell Tracking / methods
  • Disease Models, Animal
  • Disease Progression
  • Fluorescent Antibody Technique
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Genes, Reporter
  • Humans
  • Immunohistochemistry
  • Mice
  • Mice, Transgenic
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • SOXB1 Transcription Factors / genetics*
  • SOXB1 Transcription Factors / metabolism
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / metabolism

Substances

  • Biomarkers, Tumor
  • SOXB1 Transcription Factors