Aurora-A Regulates Progression and Metastasis of Colorectal Cancer by Promoting Slug Activity

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Abstract

Epithelial–mesenchymal transition (EMT) is associated with cancer metastasis and poor prognosis, but the exact mechanism has not been clarified. Centrosomal Aurora-A kinase gene is frequently overexpressed in a variety of cancers and plays a pivotal role in the growth and survival of cancer cells. However, its role in colorectal cancer metastasis has not been confirmed. Here we demonstrate that Aurora-A plays a crucial role in the progression and metastasis of colorectal cancer by regulating epithelial–mesenchymal transition. In our study, increased Aurora-A expression was detected in colorectal cancer clinical specimens compared to normal colorectal tissues. Moreover, overexpressed Aurora-A significantly promoted the proliferation, migration, and invasion capacity of colorectal cancer cells and then enhanced metastatic capacity of colorectal cancer in vitro and in vivo and eventually led to poor prognosis. Conversely, silencing Aurora-A expression in colorectal cancer cells decreased the capacity of proliferation, migration, and invasion and further reduced colorectal cancer metastasis. Mechanistically, we found that Slug was involved in Aurora-A–induced migration and invasion of colorectal cancer cells. Silencing Slug expression could block Aurora-A–induced migration, invasion, and metastasis of colorectal cancer cells. Furthermore, the expression of Aurora-A and Slug were positively correlated in colorectal cancer tissues and paired normal colorectal tissue. Taken together, our findings revealed a critical role of Aurora-A in colorectal cancer progression and metastasis by regulating epithelial–mesenchymal transition.

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