LKB1 and AMPK family signaling: the intimate link between cell polarity and energy metabolism.
Research on the LKB1 tumor suppressor protein mutated in cancer-prone Peutz-Jeghers patients has continued at a feverish pace following exciting developments linking energy metabolism and cancer development. This review summarizes the current state of research on the LKB1 tumor suppressor. The weight of the evidence currently indicates an evolutionary conserved role for the protein in the regulation of various aspects of cellular polarity and energy metabolism. We focus on studies examining the concept that both cellular polarity and energy metabolism are regulated through the conserved LKB1-AMPK signal transduction pathway. Recent studies from a variety of model organisms have given new insight into the mechanism of polyp development and cancer formation in Peutz-Jeghers patients and the role of LKB1 mutation in sporadic tumorigenesis. Conditional LKB1 mouse models have outlined a tissue-dependent context for pathway activation and suggest that LKB1 may affect different AMPK isoforms independently. Elucidation of the molecular mechanism responsible for Peutz-Jeghers syndrome will undoubtedly reveal important insight into cancer development in the larger population.
Jansen
Marnix
M
Hubrecht Institute, Developmental Biology and Stem Cell Research, 3584 CT Utrecht, The Netherlands.
Ten Klooster
Jean Paul
JP
Offerhaus
G Johan
GJ
Clevers
Hans
H
D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases / Q000502:physiology*; D000818:Animals; D016764:Cell Polarity / Q000502:physiology; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000502:physiology; D006801:Humans; D051379:Mice; D010580:Peutz-Jeghers Syndrome / Q000235:genetics / Q000503:physiopathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; C491654:Stk11 protein, mouse; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases