title: Overexpression of Rap-1A indicates a poor prognosis for oral cavity squamous cell carcinoma and promotes tumor cell invasion via Aurora-A modulation.
abstract: 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.
authors.affiliation: Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan.
authors.forename: Chang-Han
authors.initials: CH
authors.lastname: Chen
authors.forename: Hui-Ching
authors.initials: HC
authors.lastname: Chuang
authors.forename: Chao-Cheng
authors.initials: CC
authors.lastname: Huang
authors.forename: Fu-Min
authors.initials: FM
authors.lastname: Fang
authors.forename: Hsuan-Ying
authors.initials: HY
authors.lastname: Huang
authors.forename: Hsin-Ting
authors.initials: HT
authors.lastname: Tsai
authors.forename: Li-Jen
authors.initials: LJ
authors.lastname: Su
authors.forename: Li-Yen
authors.initials: LY
authors.lastname: Shiu
authors.forename: Steve
authors.initials: S
authors.lastname: Leu
authors.forename: Chih-Yen
authors.initials: CY
authors.lastname: Chien
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D064127:Aurora Kinases; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009055:Mouth / Q000201:enzymology / Q000473:pathology*; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016016:Proportional Hazards Models; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D012044:Regression Analysis; D012307:Risk Factors; D016019:Survival Analysis; D015854:Up-Regulation / Q000235:genetics; D020827:rap1 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C430803:RAP1A protein, human; D034741:RNA, Small Interfering; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D020827:rap1 GTP-Binding Proteins