Oct4 mediates tumor initiating properties in oral squamous cell carcinomas through the regulation of epithelial-mesenchymal transition

PLoS One. 2014 Jan 27;9(1):e87207. doi: 10.1371/journal.pone.0087207. eCollection 2014.

Abstract

Background: Overexpression of Oct4, an important transcription factor of embryonic stem cells (ESC), has been reported in several cancers. The aim of this study was to determine the emerging role of Oct4 in oral squamous cell carcinoma (OSCC) both in vitro and in vivo.

Methodology/principal finding: Tumourigenic activity and molecular mechanisms of Oct4 overexpression or knockdown by lentiviral infection in OSCC was investigated in vitro and in vivo. Initially, we demonstrated that Oct4 expression was increased in OSCC cell lines as compared to a normal oral epithelial cell line SG. Overexpression of Oct4 was demonstrated to enhance cell proliferation, invasiveness, anchorage-independent growth and xenotransplantation tumourigenicity. These findings were coupled with epithelial-mesenchymal transition (EMT) transformation in OSCCs. In contrast, the silence of Oct4 significantly blocked the xenograft tumorigenesis of OSCC-derived cancer stem cells (OSCC-CSCs) and significantly improved the recipient survival. Clinically, the level of Oct4 expression was higher in recurrent and metastatic OSCC specimens but lower in primary OSCC specimens.

Conclusion/significance: Our results suggest that Oct4-mediated tumorigenecity is associated with the regulation of EMT. Oct4 might be a therapeutic target for OSCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenesis / genetics*
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / physiopathology
  • Cell Line, Tumor
  • DNA Primers / genetics
  • Epithelial-Mesenchymal Transition / physiology*
  • Genetic Vectors / genetics
  • Humans
  • Mice
  • Mice, Nude
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / physiopathology
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tetrazolium Salts
  • Thiazoles

Substances

  • DNA Primers
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • Tetrazolium Salts
  • Thiazoles
  • thiazolyl blue

Grant support

This study was supported by a research grant from Chung Shan Medical University Hospital (CSH-2013-C-015) and the National Science Council (100-2632-B-040-001-MY3, 101-2314-B-040-016, 102-2628-B-040 -001 -MY3) in Taiwan, ROC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.