Evolving Lessons on the Complex Role of AMPK in Normal Physiology and Cancer

AMP kinase (AMPK) is an evolutionarily conserved enzyme required for adaptive responses to various physiological and pathological conditions. AMPK executes numerous cellular functions, some of which are often perceived at odds with each other. While AMPK is essential for embryonic growth and development, its full impact in adult tissues is revealed under stressful situations that organisms face in the real world. Conflicting reports about its cellular functions, particularly in cancer, are intriguing and a growing number of AMPK activators are being developed to treat human diseases such as cancer and diabetes. Whether these drugs will have only context-specific benefits or detrimental effects in the treatment of human cancer will be a subject of intense research. Here we review the current state of AMPK research with an emphasis on cancer and discuss the yet unresolved context-dependent functions of AMPK in human cancer.

TrendsAMP-activated protein kinase (AMPK) is an evolutionarily conserved cellular energy sensor.There are many recognized and unrecognized roles of AMPK in normal physiology and pathophysiology.Some functions of AMPK are likely beyond energy sensing.The multisubunit structure and sensitivity to various stresses confer complexity to AMPK function.Appropriate genetic models are desperately needed to understand the context-dependent role of AMPK in metabolic diseases including cancer.