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

Nat Rev Cancer. 2009 Aug;9(8):563-75. doi: 10.1038/nrc2676.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / drug effects
  • AMP-Activated Protein Kinases / physiology*
  • Animals
  • Blood Glucose / metabolism
  • Disease Models, Animal
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Mice
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein Kinases / physiology
  • Protein-Serine-Threonine Kinases / drug effects
  • Protein-Serine-Threonine Kinases / physiology*
  • Signal Transduction / physiology*
  • TOR Serine-Threonine Kinases

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Protein Kinase Inhibitors
  • Protein Kinases
  • STK11 protein, human
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • mTOR protein, mouse
  • Protein-Serine-Threonine Kinases
  • AMP-Activated Protein Kinases