eEF2K promotes progression and radioresistance of esophageal squamous cell carcinoma

To investigate the biological function of eEF2K in esophageal squamous cell carcinoma (ESCC).

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.

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).

eEF2K induced progression and radioresistance in ESCC, which may be a novel therapeutic target for ESCC to increase radiosensitivity.