Abstract
BackgroundOverexpression 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 FindingTumourigenic 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/SignificanceOur results suggest that Oct4-mediated tumorigenecity is associated with the regulation of EMT. Oct4 might be a therapeutic target for OSCC.
Highlights
Oral squamous cell carcinoma (OSCC) is the sixth most prevalent malignancy worldwide and accounts for approximately 8–10% of all cancers in Southeast Asia [1]
Expression of Oct4 in oral squamous cell carcinoma (OSCC) cell lines To understand the expression of Oct4 in OSCC cell lines (OSCCs), the endogenous protein level of Oct4 in nine established OSCC cell lines and one normal oral epithelial cell line SG was examined by real-time reverse transcription-polymerase chain reaction (RT-PCR) and western blot analyses
Accumulating data demonstrate that a cancer stem cells (CSCs) hypothesis has been bolstered by the clinical observation that malignant tumors are relatively resistant to chemo-radiotherapies [35,36]
Summary
Oral squamous cell carcinoma (OSCC) is the sixth most prevalent malignancy worldwide and accounts for approximately 8–10% of all cancers in Southeast Asia [1]. Oct is the key transcription factor that is involved in the maintenance of pluripotency and self-renewal in undifferentiated embryonic stem (ES) cells [3]. Oct has been reported to be overexpressed in various cancers including germ cell tumors [5],breast [6], cervix [7], oral [8], prostate [9], lung [10], gastric [11], brain [12], liver [13], and ovarian cancer [14]. Oct is to be a key determinant of cancer stem cells (CSCs) properties [15]. Oct mediated molecular mechanisms in OSCC still remain to be elucidated. Overexpression of Oct, 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 Oct in oral squamous cell carcinoma (OSCC) both in vitro and in vivo
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