Biological Function And Molecular Mechanism Of Mitotic Aurora-A Kinase Promoting Proliferation, Invasion And Metastasis In Human Esophageal Squamous Cell Carcinoma Cell

Worldwide, esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors. The invasive and metastatic stage of ESCC progression is a major cause of death in cancer patients. Aurora-A, a serine/threonine protein kinase, plays an important role in centrosome separation, maturation, bipolar spindle assembly and the regulation of the G₂/M transition. Increased attention has now been focused on Aurora-A kinase because of its suggestive role in tumorigenesis. It has been shown that amplification and overexpression of the Aurora-A occur in several types of human tumors, including ESCC. Aurora-A could function as a potential oncogene when it is overexpressed. Further, Aurora-A overexpression is more frequently associated with the grades of tumor differentiation and invasive capability. These observations suggest that Aurora-A overexpression correlates with the occurrence and development of ESCC. However, direct evidence for a role of Aurora-A in metastasis is currently lacking. In addition, the molecular mechanism of Aurora-A promoting invasion and metastasis in ESCC remains to be defined.To clarify whether Aurora-A could promote ESCC cells invasion and metastasis, KYSE150 cells were stably transfected with a GFP tagged full length Aurora-A expression vector, pEGFP-Aurora-A. In vitro analysis showed that the Aurora-A-transfected clones promoted tumor cells growth, increased the adhesion, migration and the Matrigel invasion compared with those transfected with vector only. Moreover, we have shown for the first time Aurora-A-transfected clones markedly stimulated subcutaneous tumor growth and enhanced spontaneous lung and lymph node metastasis compared with the vector control clones.To further confirm the role of Aurora-A in development of ESCC, the endogenous Aurora-A expression in EC9706 cells was downregulated using siRNA strategy. Then we established stable transfectants of EC9706 cells with either pGCsi-Aurora-A or pGCsi-control. The cells transfected with pGCsi-Aurora-A had reduced expression of the Aurora-A protein compared with those transfected with pGCsi-control. The knockdown of Aurora-A induced inhibition of ESCC cell growth and migration in vitro, which was consistent with our observations that Aurora-A overexpressing cells exhibited enhanced malignant phenotype.