title: SOX2 regulates self-renewal and tumorigenicity of stem-like cells of head and neck squamous cell carcinoma.
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.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: S H
authors.initials: SH
authors.lastname: Lee
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
authors.forename: S-Y
authors.initials: SY
authors.lastname: Oh
authors.affiliation: Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: S I
authors.initials: SI
authors.lastname: Do
authors.affiliation: Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Kang
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Ewha University School of Medicine, Seoul, Korea.
authors.forename: Y S
authors.initials: YS
authors.lastname: Rho
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Hallym University College of Medicine, Seoul, Korea.
authors.forename: W J
authors.initials: WJ
authors.lastname: Bae
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: Y C
authors.initials: YC
authors.lastname: Lim
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000502:physiology; D000818:Animals; D063646:Carcinogenesis; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D056744:Cyclin B1 / Q000502:physiology; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000502:physiology; D014411:Neoplastic Stem Cells / Q000473:pathology*; D055748:SOXB1 Transcription Factors / Q000502:physiology*; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C534699:CCNB1 protein, human; D056744:Cyclin B1; D009363:Neoplasm Proteins; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors