Overexpression of rap-1A indicates a poor prognosis for oral cavity squamous cell carcinoma and promotes tumor cell invasion via aurora-A modulation

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Title:	Overexpression of rap-1A indicates a poor prognosis for oral cavity squamous cell carcinoma and promotes tumor cell invasion via aurora-A modulation
Authors:	蘇立仁;Chen, Chang-Han;Chuang, Hui-Ching;Huang, Chao-Cheng;Fang, Fu-Min;Huang, Hsuan-Ying;Tsai, Hsin-Ting;Su, Li-Jen;Shiu, Li-Yen;Leu, Steve;Chien, Chih-Yen
Contributors:	生醫理工學院生醫科學與工程學系
Keywords:	Adult;Aged;Aged, 80 and over;Aurora Kinases;Carcinoma, Squamous Cell - enzymology;Carcinoma, Squamous Cell - genetics;Carcinoma, Squamous Cell - pathology;Cell Line, Tumor;Cell Movement;Female;Gene Expression Regulation, Neoplastic;Gene Knockdown Techniques;Humans;Immunohistochemistry;Male;Middle Aged;Mouth - enzymology;Mouth - pathology;Mouth Neoplasms - enzymology;Mouth Neoplasms - genetics;Mouth Neoplasms - pathology;Neoplasm Invasiveness;Pathology;Prognosis;Proportional Hazards Models;Protein Binding;Protein-Serine-Threonine Kinases - metabolism;rap1 GTP-Binding Proteins - genetics;rap1 GTP-Binding Proteins - metabolism;Regression Analysis;Risk Factors;RNA, Small Interfering - metabolism;Survival Analysis;Up-Regulation - genetics
Date:	2013-02-01
Issue Date:	2026-04-23 11:18:37 (UTC+8)
Publisher:	Elsevier Inc.;United States: Elsevier Inc
Abstract:	摘要： 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. 其他題名： Am J Pathol 出版者： United States: Elsevier Inc 出版日期： 2013-02-01 出處： The American Journal of Pathology, 2013-02, Vol.182 (2), p.516-528 資源來源： Elsevier ScienceDirect Journals Complete 版權： 2013 American Society for Investigative Pathology 版權： American Society for Investigative Pathology 版權： Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. 識別號： ISSN: 0002-9440 識別號： ISSN: 1525-2191 識別號： EISSN: 1525-2191 識別號： DOI: 10.1016/j.ajpath.2012.10.023 識別號： PMID: 23219753
Appears in Collections:	[Department of Biomedical Sciences and Engineering ] journal & Dissertation

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