title: Sox2 expression involvement in the oncogenicity and radiochemoresistance of oral cancer stem cells.
abstract: OBJECTIVE
  Sox2, a high-mobility-group DNA binding protein, is part of the key set of transcription factors that are involved in the maintenance of pluripotency and self-renewal in undifferentiated stem cells. A recent study has further suggested cancer stem cells (CSCs) are key contributors to radiochemoresistance and are responsible for oral squamous cell carcinoma (OSCC) progression. The aim of this study was to determine the emerging role of Sox2 in radiochemosensitivity of oral CSCs.
  
  
  METHODS
  We determined the function of Sox2 on oncogenicity and radiochemosensitivity of OSCC by overexpression or silencing Sox2 in vitro and in vivo.
  
  
  RESULTS
  Initially, Sox2 expression was increased in OSCC cell lines and OSCC specimens. Upregulated Sox2 is correlated with poor survival outcome of OSCC patients. Overexpression of Sox2 was demonstrated to enhance invasiveness, anchorage-independent growth, xenotransplantation tumourigenicity in OSCC cells. Targeting Sox2 to spheroid cells (SC) and ALDH1+CD44+ cells from OSCC significantly inhibited their CSCs and tumorigenic abilities. Down regulation of SOX2 in OSCC-SC was found to repress invasiveness and diminish epithelail-mesenchymal transition (EMT) traits. Furthermore, silencing Sox2 effectively suppressed the expression of drug-resistance and anti-apoptotic genes and increased the sensitivity of the cells to radiation combined cisplatin treatment. Finally, the in vivo therapeutic efficacy of targeting Sox2 synergistically suppressed tumorigenesis and improved the survival rate when used in combination with radiotherapy and cisplatin in OSCC-SC-transplanted immunocompromised mice.
  
  
  CONCLUSIONS
  Sox2-mediated CSCs property is associated with the regulation of EMT and Sox2 s as therapeutic target in OSCC.
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan; Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Ming-Yung
authors.initials: MY
authors.lastname: Chou
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Fang-Wei
authors.initials: FW
authors.lastname: Hu
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Chuan-Hang
authors.initials: CH
authors.lastname: Yu
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan; Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan. Electronic address: ccyu@csmu.edu.tw.
authors.forename: Cheng-Chia
authors.initials: CC
authors.lastname: Yu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers; D019008:Drug Resistance, Neoplasm; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D017931:DNA Primers; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors
keywords: Cancer stem cells; EMT; Oral squamous cell carcinoma (OSCC); Radiochemoresistance; Sox2