title: Aurora-A enhances malignant development of esophageal squamous cell carcinoma (ESCC) by phosphorylating β-catenin.
abstract: The Aurora-A gene encodes a serine/threonine protein kinase that is frequently overexpressed 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 β-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 β-catenin and phosphorylates β-catenin at Ser552 and Ser675. Substitutions of serine residue with alanine at single or both positions substantially attenuate Aurora-A-mediated stabilization of β-catenin, abolish its cytosolic and nuclear localization as well as transcriptional activity. In addition, Aurora-A overexpression is significantly correlated with increased cytoplasmic β-catenin expression in ESCC tissues. In view of our results, we propose that Aurora-A-mediated phosphorylation of β-catenin is a novel mechanism of malignancy development of tumor.
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.17 Panjiayuan South Road, Chaoyang District, Beijing 10021, PR China; Department of Radiation Oncology, University of Pittsburgh School of Medicine, Cancer Institute, Pittsburgh, PA 15213, USA.
authors.forename: Shunqian
authors.initials: S
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.17 Panjiayuan South Road, Chaoyang District, Beijing 10021, PR China; Department of Biochemistry and Molecular Biology, Shanxi Medical University, No. 56 South Road of Xinjian, Taiyuan 030001, PR China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.17 Panjiayuan South Road, Chaoyang District, Beijing 10021, PR China.
authors.forename: Tong
authors.initials: T
authors.lastname: Tong
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.17 Panjiayuan South Road, Chaoyang District, Beijing 10021, PR China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.17 Panjiayuan South Road, Chaoyang District, Beijing 10021, PR China.
authors.forename: Ji
authors.initials: J
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.17 Panjiayuan South Road, Chaoyang District, Beijing 10021, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.17 Panjiayuan South Road, Chaoyang District, Beijing 10021, PR China. Electronic address: zhanqimin@pumc.edu.cn.
authors.forename: Qimin
authors.initials: Q
authors.lastname: Zhan
mesh_terms: D064096:Aurora Kinase A / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000235:genetics; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D009363:Neoplasm Proteins; D051176:beta Catenin; C576917:AURKA protein, human; D064096:Aurora Kinase A
keywords: Aurora-A; Esophageal squamous cell carcinoma (ESCC); β-catenin