Breast cancer (BC) is the most common neoplasm in women worldwide, and metastatic mammary tumours account for more than 40% of all cancer-related deaths in females. Novel and effective therapies targeting the invasive spread of BC are therefore urgently needed.
During tumorigenesis, rapidly proliferating cancer cells outstrip locally available oxygen and nutrient supplies creating an environment of nutritional and energetic stress. Tumour cells which can adapt to these challenges emerge as more advanced and aggressive clones driving tumour progression to a more aggressive phenotype.
eEF2K is an atypical protein kinase which inhibits the elongation stage of protein synthesis. It has recently emerged as a key player in tumour adaptation to nutrient and energy limitation. eEF2K is not essential for normal tissue development/homeostasis but functions under diverse stress conditions
Using compound eEF2K KO–PyMT transgenic mouse model, we have found that eEF2K is indispensable for mammary cancer progression to the advanced, invasive stage. Relevance of these findings to human disease was also established. Furthermore, we have uncovered novel molecular mechanisms by which eEF2K is activated during the process of mammary tumorigenesis. Most importantly, we have demonstrated for the first time the potential of eEF2K inhibition for therapeutic intervention in advanced primary breast cancers.