The eEF2 Kinase Shapes Cellular Adaption of Medulloblastoma to Metabolic Stress

During tumour progression, tumour cells are exposed to metabolic stress, such as nutrient deprivation, due to abnormal tumour vasculature. The ability of tumour cells to respond and manage reduced nutrient availability is critical for outcome. The molecular pathways supporting metabolic adaptation of tumour cells to nutrient stress need to be better defined, especially since they represent potential therapeutic targets. We report that the translation elongation factor 2 (eEF2) kinase, a major regulator of protein synthesis, mediates tumour adaptation to nutrient starvation. Ablation of eEF2K expression sensitizes aggressive human tumour cells, such as medulloblastoma (MB) cells, to nutrient removal. In addition, analysis of gene expression in MB show that eEF2K expression is upregulated in the most aggressive subgroup, namely group 3, and that high eEF2K expression is strongly associated with poor survival. Finally, our data reveal that eEF2K is in fact an evolutionarily conserved mediator of the physiological response to nutrient starvation, as genetic removal of eEF2K compromises survival of C. elegans in absence of nutrients. Overall, our work highlights a novel component of the survival response to nutrient deprivation which is hijacked by MB tumour cells to support their adaptation to nutrient stress.