期刊
AMERICAN JOURNAL OF PATHOLOGY
卷 182, 期 2, 页码 516-528出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2012.10.023
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类别
资金
- Kaohsiung Chang Gung Memorial Hospital, Taiwan [CMRPG890091, CMRPG870411-870413, CMRPG890921, CMRPG8A0391-8A0392]
- National Science Council [NSC-98-2314-B-182A-042-MY3, NSC-98-2314-B-182A-065, NSC 100-2320-B-182A-001]
- Chang Gung Medical Foundation at the Kaohsiung Chang Gong Memorial Hospital Tissue Bank
- [CLRPG871342similar to871343]
- [CLRPG870463]
- [CMRP0870461]
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. (Am J Pathol 2013, 182: 516-528; http://dx.doi.org/10.1016/j.ajpath.2012.10.023)
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