Abstract
Mengyang Zhao1,2,*, Weiyi Fang1,2,*, Yan Wang2,5,*, Suiqun Guo6,*, Luyun Shu6, Lijing Wang2,6, YiYu Chen2, Qiaofen Fu2, Yan Liu2, Shengni Hua2, Yue Fan2, Yiyi Liu2, Xiaojie Deng2, Rongcheng Luo1, Zhong Mei5, Qinping Jiang2,4, Zhen Liu2,3
1Cancer Center, Traditional Chinese Medicine-Integrated Hospital of Southern Medical University, Guangzhou, Guangdong, China
2Cancer Research Institute, Southern Medical University, Guangzhou, China
3Department of Pathology of Basic School, Medical University of Guangzhou, Guangzhou, China
4Department of Pathology, Third Affiliated Hospital of Guangzhou Medical College, Guangzhou, China
5Department of Obstetrics and Gynecology of Nanfang Hospital, Southern Medical University, Guangzhou, China
6Department of Obstetrics and Gynecology, the Third Affiliated Hospital of Southern Medical University, Guangzhou, China
*These authors have contributed equally to this work
Correspondence to:
Weiyi Fang, e-mail: fangweiyi1975@163.com
Zhen Liu, e-mail: narcissus_jane@163.com
Qingping Jiang, e-mail: 413430005@qq.com
Keywords: ENO1, endometrial carcinoma, cell growth, EMT, glycolysis
Received: December 30, 2014 Accepted: April 10, 2015 Published: April 24, 2015
ABSTRACT
ENO1 plays a paradoxical role in driving the pathogenesis of tumors. However, the clinical significance of ENO1 expression remains unclear and its function and modulatory mechanisms have never been reported in endometrial carcinoma (EC). In this study, ENO1 silencing significantly reduced cell glycolysis, proliferation, migration, and invasion in vitro, as well as tumorigenesis and metastasis in vivo by modulating p85 suppression. This in turn mediated inactivation of PI3K/AKT signaling and its downstream signals including glycolysis, cell cycle progression, and epithelial-mesenchymal transition (EMT)-associated genes. These effects on glycolysis and cell growth were not observed after ENO1 suppression in normal human endometrial epithelial cells (HEEC). Knocking down ENO1 could significantly enhance the sensitivity of EC cells to cisplatin (DDP) and markedly inhibited the growth of EC xenografts in vivo. In clinical samples, EC tissues exhibited higher expression levels of ENO1 mRNA and protein compared with normal endometrium tissues. Patients with higher ENO1 expression had a markedly shorter overall survival than patients with low ENO1 expression. We conclude that ENO1 favors carcinogenesis, representing a potential target for gene-based therapy.
