The LKB1 tumor suppressor kinase in human disease.
Inactivating germline mutations in the LKB1 gene underlie Peutz-Jeghers syndrome characterized by hamartomatous polyps and an elevated risk for cancer. Recent studies suggest the involvement of LKB1 also in more common human disorders including diabetes and in a significant fraction of lung adenocarcinomas. These observations have increased the interest towards signaling pathways of this tumor suppressor kinase. The recent breakthroughs in understanding the molecular functions of the LKB1 indicate its contribution as a regulator of cell polarity, energy metabolism and cell proliferation. Here we review how the substrates and cellular functions of LKB1 may be linked to Peutz-Jeghers syndrome and other diseases, and discuss how some of the molecular changes associated with altered LKB1 signaling might be used in therapeutic approaches.
Katajisto
Pekka
P
Molecular Cancer Biology Program, Translational Genome-Scale Biology and Institute of Biomedicine, Biomedicum Helsinki, University of Helsinki, Finland.
Vallenius
Tea
T
Vaahtomeri
Kari
K
Ekman
Niklas
N
Udd
Lina
L
Tiainen
Marianne
M
Mäkelä
Tomi P
TP
D000091162:AMP-Activated Protein Kinase Kinases; D000230:Adenocarcinoma / Q000235:genetics; D000818:Animals; D016764:Cell Polarity / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics; D051379:Mice; D010580:Peutz-Jeghers Syndrome / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D011494:Protein Kinases / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000502:physiology*
D052246:Cyclooxygenase 2 Inhibitors; D025521:Tumor Suppressor Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases