AMPK regulated metabolic programing: oncogenic or growth suppressive? Evolving lessons from genetic and pharmacologic studies

Background Cancer cells reprogram their metabolism for optimal growth and survival. Identifying the genes and their functions crucial for cancer metabolic reprograming might have therapeutic implications. The multifunctional kinase AMPK is an evolutionarily conserved energy sensor that plays an important role in cell proliferation, growth and survival. It remains unclear whether AMPK functions as a tumor suppressor or a contextual oncogene. This is because while on one hand active AMPK inhibits mTOR and lipogenesis two crucial arms of cancer growth, AMPK also ensures viability during metabolic stress. Many studies have shown that AMPK activation by two indirect AMPK agonists AICAR and metformin (now in many cancer clinical trials) reduces cancer cell proliferation an effect that is rescued by an AMPK inhibitor Compound C in some studies. We used genetic models to scrutinize the specificity of these reagents and examine whether AMPK is a growth suppressor in glioblastoma.