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

被引:20
作者
Jin, Shunqian [1 ,2 ,3 ]
Wang, Xiaoxia [1 ,2 ,4 ]
Tong, Tong [1 ,2 ]
Zhang, Dongdong [1 ,2 ]
Shi, Ji [1 ,2 ]
Chen, Jie [1 ,2 ]
Zhan, Qimin [1 ,2 ]
机构
[1] Chinese Acad Med Sci, State Key Lab Mol Oncol, Canc Inst & Hosp, Beijing 100021, Peoples R China
[2] Peking Union Med Coll, Beijing 100021, Peoples R China
[3] Univ Pittsburgh, Inst Canc, Dept Radiat Oncol, Sch Med, Pittsburgh, PA 15213 USA
[4] Shanxi Med Univ, Dept Biochem & Mol Biol, Taiyuan 030001, Peoples R China
基金
中国国家自然科学基金;
关键词
Aurora-A; beta-catenin; Esophageal squamous cell carcinoma (ESCC); NEGATIVE REGULATOR; KINASE; CANCER; OVEREXPRESSION; AMPLIFICATION; SURVIVAL; PATHWAY; GENE; AXIN;
D O I
10.1016/j.molonc.2014.08.002
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:249 / 259
页数:11
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