title: Oct4 is a critical regulator of stemness in head and neck squamous carcinoma cells.
abstract: Cancer stem cells (CSCs) have been suggested as responsible for the initiation and progression of cancers. Octamer-binding transcription factor 4 (Oct4) is an important regulator of embryonic stem cell fate. Here, we investigated whether Oct4 regulates stemness of head and neck squamous carcinoma (HNSC) CSCs. Our study showed that ectopic expression of Oct4 promotes tumor growth through cyclin E activation, increases chemoresistance through ABCC6 expression and enhances tumor invasion through slug expression. Also, Oct4 dedifferentiates differentiated HNSC cells to CSC-like cells. Furthermore, Oct4(high) HNSC CSCs have more stem cell-like traits compared with Oct4(low) cells, such as self-renewal, stem cell markers' expression, chemoresistance, invasion capacity and xenograft tumorigeneity in vitro and in vivo. In addition, knockdown of Oct4 led to markedly lower HNSC CSC stemness. Finally, there was a significant correlation between Oct4 expression and survival of 119 HNSC patients. Collectively, these data suggest that Oct4 may be a critical regulator of HNSC CSCs and its targeting may be potentially valuable in the treatment of HNSC CSCs.
authors: Department of Otolaryngology-Head and Neck Surgery, Cancer Research Institute, Daejeon, Korea.
authors: B S
authors: BS
authors: Koo
authors: Department of Otorhinolaryngology-Head and Neck Surgery, Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Seoul, Korea.
authors: S H
authors: SH
authors: Lee
authors: Research Institute for Medical Sciences and Pathology, Chungnam National University College of Medicine, Daejeon, Korea.
authors: J M
authors: JM
authors: Kim
authors: Research Institute for Medical Sciences and Pathology, Chungnam National University College of Medicine, Daejeon, Korea.
authors: S
authors: S
authors: Huang
authors: Department of Otolaryngology-Head and Neck Surgery, Cancer Research Institute, Daejeon, Korea.
authors: S H
authors: SH
authors: Kim
authors: Department of Otorhinolaryngology-Head and Neck Surgery, Ewha University School of Medicine, Seoul, Korea.
authors: Y S
authors: YS
authors: Rho
authors: Department of Otolaryngology-Head and Neck Surgery, Hallym University College of Medicine, Seoul, Korea.
authors: W J
authors: WJ
authors: Bae
authors: Department of Otorhinolaryngology-Head and Neck Surgery, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Korea.
authors: H J
authors: HJ
authors: Kang
authors: Department of Otorhinolaryngology-Head and Neck Surgery, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Korea.
authors: Y S
authors: YS
authors: Kim
authors: Department of Otorhinolaryngology-Head and Neck Surgery, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Korea.
authors: J H
authors: JH
authors: Moon
authors: Department of Otorhinolaryngology-Head and Neck Surgery, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Korea.
authors: Y C
authors: YC
authors: Lim
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D019927:Cyclin E / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D000071250:Snail Family Transcription Factors; D016019:Survival Analysis; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D019927:Cyclin E; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D050814:Octamer Transcription Factor-3; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C102029:ABCC6 protein, human; C494173:POU5F1 protein, human; C000604407:SNAI1 protein, human; C000604449:Snai2 protein, mouse