EEF2K promotes progression and radioresistance of esophageal squamous cell carcinoma. Issue 3 (September 2017)

• Record Type: Journal Article
• Authors: Zhu, Hongcheng; Song, Hongmei; Chen, Guangzong; Yang, Xi; Liu, Jia; Ge, Yangyang; Lu, Jing; Qin, Qin; Zhang, Chi; Xu, Liping; Di, Xiaoke; Cai, Jing; Ma, Jianxin; Zhang, Shu; Sun, Xinchen
• Is Part Of: Radiotherapy and oncology. Volume 124:Issue 3(2017:Sep.)
• Page Start: 439
• Page End: 447
• Publication Date: 2017-09
• Subjects: Eukaryotic elongation factor 2 kinase -- Esophageal squamous cell carcinoma -- Radiosensitivity -- Autophagy -- Apoptosis -- Tumor growth; Oncology -- Periodicals; Radiotherapy -- Periodicals; Tumors -- Periodicals; Medical Oncology -- Periodicals; Neoplasms -- radiotherapy -- Periodicals; Radiotherapy -- Periodicals; Radiothérapie -- Périodiques; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9940642
• DOI: 10.1016/j.radonc.2017.04.001
• Languages: English
• ISSNs: 0167-8140

Abstract

Abstract: Objectives: To investigate the biological function of eEF2K in esophageal squamous cell carcinoma (ESCC). Materials and methods: Tissue microarrays containing 100 pairs of ESCC tumor and adjacent normal tissues were completed. Overexpression and knockdown of eEF2K were constructed in ECA-109 and TE-13 ESCC cells. DNA damage, cell viability, migration and invasion, radioresistance, apoptosis and autophagy were determined by immunofluorescence, CCK-8, transwell assay, colony formation assay, flow cytometry and western blot, respectively. Tumor growth and radioresistance were also evaluated using xenograft models created in nude mice. Results: eEF2K expression was higher in ESCC tissues compared with matched non-tumor tissues ( P < 0.05). Proliferation was increased in eEF2K overexpressing cells compared with controls ( P < 0.05), while silencing eEF2K reduced cell proliferation ( P < 0.05). Furthermore, lower levels of eEF2K expression correlated with slower migration and invasion rates ( P < 0.05), while higher levels of eEF2K expression with faster migration and invasion rates ( P < 0.05). eEF2K overexpression resulted in radioresistance and radiation-induced autophagy, and reduced radiation-induced apoptosis compared with controls, but silencing eEF2K promoted radiosensitivity and apoptosis, and reduced autophagy. In addition, eEF2K overexpression promoted the tumor growth in vivo ( P < 0.01). Combined treatment of NH125 (a pharmacological inhibitor of eEF2K) and radiation was more effective at delaying xenograft tumor growth than NH125 and radiation alone ( P < 0.05). Conclusion: eEF2K induced progression and radioresistance in ESCC, which may be a novel therapeutic target for ESCC to increase radiosensitivity.