The LKB1–AMPK pathway: metabolism and growth control in tumour suppression

The human tumour suppressor LKB1 directly phosphorylates and activates AMPK, a central metabolic sensor. AMPK is a key therapeutic target in patients with diabetes, and the connection between AMPK and several tumour suppressors suggests that therapeutic manipulation of this pathway using established diabetes drugs warrants investigation in patients with cancer. In the past decade, studies of the human tumour suppressor LKB1 have uncovered a novel signalling pathway that links cell metabolism to growth control and cell polarity. LKB1 encodes a serine–threonine kinase that directly phosphorylates and activates AMPK, a central metabolic sensor. AMPK regulates lipid, cholesterol and glucose metabolism in specialized metabolic tissues, such as liver, muscle and adipose tissue. This function has made AMPK a key therapeutic target in patients with diabetes. The connection of AMPK with several tumour suppressors suggests that therapeutic manipulation of this pathway using established diabetes drugs warrants further investigation in patients with cancer.