Overexpression of Rap-1A Indicates a Poor Prognosis for Oral Cavity Squamous Cell Carcinoma and Promotes Tumor Cell Invasion via Aurora-A Modulation
pmid: 23219753
Overexpression of Rap-1A Indicates a Poor Prognosis for Oral Cavity Squamous Cell Carcinoma and Promotes Tumor Cell Invasion via Aurora-A Modulation
The functions of Rap-1A in oral carcinogenesis are largely unexplored. In this study, we examined the expression of Rap-1A at different malignant stages of oral cavity squamous cell carcinoma (OCSCC). Semiquantitative RT-PCR, quantitative RT-PCR, and Western blotting were used to evaluate Rap-1A mRNA and protein expressions, respectively, in paired OCSCC patient specimens. To determine the possible correlation between Rap-1A expression and various clinical characteristics, 256 samples from patients with OCSCC were evaluated by immunohistochemical staining. Strong Rap-1A expression was a significant prognostic marker and predictor of aggressive OCSCC. The overall and disease-specific 5-year survival rates were significantly correlated with strong expression of Rap-1A (P < 0.001). Functionally, overexpressed Rap-1A could promote oral cancer cell migration and invasion by Transwell chambers and wound healing assay. Conversely, the suppression of Rap-1A expression using Rap-1A-mediated siRNA was sufficient to decrease cell motility. Furthermore, our data also illustrated that Aurora-A could not only induce mRNA and protein expressions of Rap-1A for enhancing cancer cell motility but also co-localize and form a complex with Rap-1A in the oral cancer cell line. Finally, immunohistochemical staining, indirect immunofluorescence, and Western blotting analysis of human aggressive OCSCC specimens revealed a significantly positive correlation between Rap-1A and Aurora-A expression. Taken together, our results suggest that the Aurora-A/Rap-1A pathway is associated with survival, tumor progression, and metastasis of OCSCC patients.
- Memorial Hospital of South Bend United States
- Chang Bing Show Chwan Memorial Hospital Taiwan
- University System of Taiwan Taiwan
- National Central University Taiwan
- Kaohsiung Chang Gung Memorial Hospital Taiwan
Adult, Aged, 80 and over, Male, Mouth, Middle Aged, Prognosis, Immunohistochemistry, Gene Expression Regulation, Neoplastic, Aurora Kinases, Cell Movement, Cell Line, Tumor, Gene Knockdown Techniques, Carcinoma, Squamous Cell, Humans, Female, Mouth Neoplasms, Neoplasm Invasiveness, Aged, Proportional Hazards Models, Protein Binding
Adult, Aged, 80 and over, Male, Mouth, Middle Aged, Prognosis, Immunohistochemistry, Gene Expression Regulation, Neoplastic, Aurora Kinases, Cell Movement, Cell Line, Tumor, Gene Knockdown Techniques, Carcinoma, Squamous Cell, Humans, Female, Mouth Neoplasms, Neoplasm Invasiveness, Aged, Proportional Hazards Models, Protein Binding
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