Cells within poorly vascularised tumours need to adapt to the lack of nutrients in order to survive. Protein synthesis is one of the most resource-intensive processes in the cell, using up to 30% of metabolic energy. The atypical enzyme eukaryotic elongation factor 2 kinase (eEF2K) negatively regulates the elongation stage of mRNA translation, the step which uses >99% of the energy and amino acids used in protein synthesis.
eEF2K is activated under conditions of low energy (via the AMP-activated protein kinase, AMPK), by low amino acid levels (through mammalian target of rapamycin complex 1 signalling) and during hypoxia.
Multiple lines of evidence show that eEF2K enables cancer cells to survive episodes of nutrient deficiency by slowing down protein synthesis. Consistent with this, inhibition or knockdown of eEF2K impairs tumour growth in vivo.
Because it controls mRNA translation, eEF2K can regulate the synthesis of specific proteins. Some of these are cytoskeletal proteins or proteins that control the cytoskeleton. Consistent with this, eEF2K also plays a role in promoting the migration and invasion of cancer cells.
Given these findings, and since eEF2K is not essential for organismal viability, there is substantial interest in the potential utility of eEF2K as a target in cancer therapy.