Aurora-A transcriptional silencing and Vincristine treatment show a synergistic effect in human tumor cells

Abstract

Aurora-A is a centrosome-associated serine/threonine kinase that is overexpressed in multiple types of human tumors. Primarily, Aurora-A functions in centrosome maturation and mitotic spindle assembly. Overexpression of Aurora-A induces centrosome amplification and G(2)/M cell-cycle progression. Recently, it was observed that overexpression of Aurora-A renders cells resistant to cisplatin (CDDP)-, etoposide, and paclitaxel-induced apoptosis. Our results indicate that already in initial stages of cancer progression Aurora-A overexpression could have a major role in inducing supernumerary centrosomes and aneuploidy, as shown by immunohistochemistry on tissue sections from various stages of human colon cancer. Aneuploidy was also observed after Aurora-A ectopic overexpression in colon cancer cells with MIN phenotype. Silencing of Aurora-A by RNA interference in tumor cell lines triggered arrest of the cell cycle associated to apoptosis/mitotic catastrophe. Finally, Aurora-A transcriptional silencing seems to confer cancer cells a greater sensitivity to chemotherapy by vincristine, indicating Aurora-A as a possible gene target in cancer therapy.