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Abstract Background Eukaryotic elongation factor-2 kinase (eEF2K) is a Ca 2+ /calmodulin (CaM)-dependent protein kinase that inhibits protein synthesis. However, the role of eEF2K in cancer development was reported paradoxically and remains to be elucidated. Methods Herein, A549 cells with eEF2K depletion or overexpression by stably transfected lentivirus plasmids were used in vitro and in vivo study. MTT and colony assays were used to detect cell proliferation and growth. Extracellular glucose and lactate concentration were measured using test kit. Immunoblot and co-immunoprecipitation assays were used to examine the molecular biology changes and molecular interaction in these cells. LC-MS/MS analysis and [γ- 32 P] ATP kinase assay were used to identify combining protein and phosphorylation site. Nude mice was utilized to study the correlation of eEF2K and tumor growth in vivo. Results We demonstrated that eEF2K inhibited lung cancer cells proliferation and affected the inhibitory effects of EGFR inhibitor gefitinib. Mechanistically, we showed that eEF2K formed a complex with PKM2 and STAT3, thereby phosphorylated PKM2 at T129, leading to reduced dimerization of PKM2. Subsequently, PKM2 impeded STAT3 phosphorylation and STAT3-dependent c-Myc expression. eEF2K depletion promoted the nuclear translocation of PKM2 and increased aerobic glycolysis reflected by increased lactate secretion and glucose. Conclusions Our findings define a novel mechanism underlying the regulation of cancer cell proliferation by eEF2K independent of its role in protein synthesis, disclosing the diverse roles of eEF2K in cell biology, which lays foundation for the development of new anticancer therapeutic strategies.

Aims and objectives To examine the prevalence of post-traumatic stress disorder symptoms and to explore the predictive factors of post-traumatic stress disorder symptoms among bereaved adolescents four years after the Yushu earthquake. Background On 14 April 2010, the 7·1-magnitude Yushu earthquake occurred in the high-altitude, hypoxia-prone regions primarily inhabited by ethnic minorities. Many adolescents lost their parents during the earthquake. This study examined post-traumatic stress disorder and its predictors among bereaved Tibetan adolescents four years after the trauma in China. Design This was a cross-sectional descriptive study. Methods This study used a cross-sectional design with 830 bereaved adolescents. Participant demographic data included gender, age and grade, and the earthquake exposure variables included the deceased relatives, whether they were buried, injured or amputated (non-life-threatening) and whether they witnessed a burial, injury or death. The post-traumatic stress disorder Checklist-Civilian version was used to assess the symptoms and prevalence of post-traumatic stress disorder, and the Coping Style Scale assessed coping styles. Results The results indicated that the prevalence of post-traumatic stress disorder was 19·3%. Individuals who were buried, injured or amputated (non-life-threatening), who witnessed a burial, injury or death, who suffered severe property loss during the earthquake and who had negative coping skills were the most likely individuals to have post-traumatic stress disorder symptoms. Conclusions The presence of post-traumatic stress disorder was very prevalent among adolescents four years after the Yushu earthquake. Effective mental health services should be developed to facilitate postdisaster recovery for bereaved adolescents at high risk for post-traumatic stress disorder. Relevance to clinical practice The findings in this study improve our understanding of post-traumatic stress disorder and related risk factors in bereaved adolescents in non-Western communities, providing useful information for rebuilding and relief work. [ABSTRACT FROM AUTHOR]