Enolase-1 is a therapeutic target in endometrial carcinoma.

// Mengyang Zhao 1, 2, * , Weiyi Fang 1, 2, * , Yan Wang 2, 5, * , Suiqun Guo 6, * , Luyun Shu 6 , Lijing Wang 2, 6 , YiYu Chen 2 , Qiaofen Fu 2 , Yan Liu 2 , Shengni Hua 2 , Yue Fan 2 , Yiyi Liu 2 , Xiaojie Deng 2 , Rongcheng Luo 1 , Zhong Mei 5 , Qinping Jiang 2, 4 , Zhen Liu 2, 3 1 Cancer Center, Traditional Chinese Medicine-Integrated Hospital of Southern Medical University, Guangzhou, Guangdong, China 2 Cancer Research Institute, Southern Medical University, Guangzhou, China 3 Department of Pathology of Basic School, Medical University of Guangzhou, Guangzhou, China 4 Department of Pathology, Third Affiliated Hospital of Guangzhou Medical College, Guangzhou, China 5 Department of Obstetrics and Gynecology of Nanfang Hospital, Southern Medical University, Guangzhou, China 6 Department 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.