Aurora-A enhances malignant development of esophageal squamous cell carcinoma (ESCC) by phosphorylating β-catenin

The Aurora-A gene encodes a serine/threonine protein ldnase that is frequently over-expressed in several types of human tumors. The overexpression of Aurora-A has been observed to associate with the grades of differentiation, invasive capability and distant lymph node metastasis of esophageal squamous cell carcinoma (ESCC). However, the molecular mechanism by which Aurora-A promotes malignant development of ESCC is still largely unknown. In this study, we show that Aurora-A overexpression enhances tumor cell invasion and metastatic potential in vitro and in vivo. Furthermore, Aurora-A overexpression inhibits the degradation of beta-catenin, promotes its dissociation from cell cell contacts and increases its nuclear translocation. We also demonstrate for the first time that Aurora-A directly interacts with beta-catenin and phosphorylates beta-catenin at Ser552 and Ser675. Substitutions of serine residue with alanine at single or both positions substantially attenuate Aurora-A-mediated stabilization of beta-catenin, abolish its cytosolic and nuclear localization as well as transcriptional activity. In addition, Aurora-A overexpression is significantly correlated with increased cytoplasmic beta-catenin expression in ESCC tissues. In view of our results, we propose that Aurora-A-mediated phosphorylation of beta-catenin is a novel mechanism of malignancy development of tumor. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.