SOX2 regulates self-renewal and tumorigenicity of stem-like cells of head and neck squamous cell carcinoma

Br J Cancer. 2014 Nov 25;111(11):2122-30. doi: 10.1038/bjc.2014.528. Epub 2014 Oct 16.

Abstract

Background: Head and neck squamous cell carcinomas (HNSCCs) display cellular heterogeneity and contain cancer stem cells (CSCs). Sex-determining region Y [SRY]-box (SOX)2 is an important regulator of embryonic stem cell fate and is aberrantly expressed in several types of human tumours. Nonetheless, the role of SOX2 in HNSCC remains unclear.

Methods: We created cells ectopically expressing SOX2 from previously established HNSCC cells and examined the cell proliferation, self-renewal capacity, and chemoresistance of these cells compared with control cells. In addition, we knocked down SOX2 in primary spheres obtained from HNSCC tumour tissue and assessed the attenuation of stemness-associated traits in these cells in vitro and in vivo. Furthermore, we examined the clinical relevance of SOX2 expression in HNSCC patients.

Results: SOX2 is aberrantly expressed in primary tissue of HNSCC patients but not in healthy tissue. SOX2 expression correlated with tumour recurrence and poor prognosis of HNSCC patients. Ectopic expression of SOX2 induced cell proliferation via cyclin B1 expression and stemness-associated features, such as self-renewal and chemoresistance. In addition, a knockdown of SOX2 in HNSCC CSCs attenuated their self-renewal capacity, chemoresistance (through ABCG2 suppression), invasion capacity (via snail downregulation), and in vivo tumorigenicity.

Conclusions: These results suggest that SOX2 may have important roles in the 'stemness' and progression of HNSCC. Targeting SOX2-positive tumour cells (CSCs) could be a new therapeutic strategy in HNSCCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / physiology
  • Animals
  • Carcinogenesis
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin B1 / physiology
  • Drug Resistance, Neoplasm
  • Epithelial-Mesenchymal Transition
  • Head and Neck Neoplasms / drug therapy
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / pathology*
  • Humans
  • Mice
  • Neoplasm Invasiveness
  • Neoplasm Proteins / physiology
  • Neoplastic Stem Cells / pathology*
  • SOXB1 Transcription Factors / physiology*
  • Squamous Cell Carcinoma of Head and Neck

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • CCNB1 protein, human
  • Cyclin B1
  • Neoplasm Proteins
  • SOX2 protein, human
  • SOXB1 Transcription Factors