Abstract
The clinical significances, cellular effects, and molecular mechanisms by which Aurora-A mediate its invasive effects in HNSCC are still unclear. Here, we found that Aurora-A expression is significantly higher in tumor tissues on 14-microarray of HNSCC in Oncomine-databases. The activity of Aurora-A was not only found in HNSCC specimens, but also significantly correlated with advanced-T-classification, positive-N-classification, TNM-stage and the poor 5-year survival rate. HNSCC-microarray profile showed that osteopontin and Aurora-A exhibited positive correlation. Stimulation of HNC cells with osteopontin results in an increase in Aurora-A expression where localized at the centrosome. Functionally, Aurora-A had the abilities to stimulate cell motility in HNC cells through increase ERK1/2 activity under osteopontin stimulation. Conversely, depletion of Aurora-A expression by siRNAs suppressed ERK1/2 activity as well as inhibition of cell invasiveness. Treatment with anti-CD44 antibodies in HNC cells not only caused a decrease of mRNA/protein of Aurora-A and ERK1/2 activity upon osteopontin stimulation, but also affected the abilities of Aurora-A-elicited cell motility. Finally, immunohistochemical/Western-blotting analysis of human aggressive HNSCC specimens showed a significant positively correlation between osteopontin-Aurora-A and ERK1/2. These findings suggest that Aurora-A is not only an important prognostic factor but also a new therapeutic target in the osteopontin/CD44/ERK pathway for HNSCC treatment.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is common malignancy, and is cited as being the sixth most ordinary cancer worldwide
Increased expression of Aurora-A and its activity positively correlated with high-stage malignant HNSCC
To further evaluate the potential role of Aurora-A in HNSCC progression, first, we analyzed the expression of Aurora-A by semi-quantitative RT-PCR and real-time RT-PCR in 8-paired HNSCC specimens with early and advanced stages
Summary
Head and neck squamous cell carcinoma (HNSCC) is common malignancy, and is cited as being the sixth most ordinary cancer worldwide. Several studies demonstrated that there is a positively correlation between Aurora-A expression and clinical aggressiveness, such as poorly differentiated tumor grade, and invasion in several cancers [5, 10,11,12,13],; some studies showed no correlation or an inverse correlation[10, 14,15,16]. These results suggested that the expression profile of Aurora-A and clinical significant in malignant cancers remains controversial. The exact molecular mechanism underlying the induction of invasion by the Aurora-A in head and neck cancer cells; has not been defined yet
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