PTEN at the crossroad of metabolic diseases and cancer in the liver.
The tumor suppressor PTEN is a phosphoinositide phosphatase regulating the PI3K/Akt signaling pathways and mutated or deleted in a variety of human cancers. Recent evidence indicates that dysregulated PTEN expression and activity in the liver critically affect hepatic insulin sensitivity and trigger the development of non-alcoholic fatty liver diseases. As well, PTEN expression/activity is also affected with HBV and HCV infection, or following alcohol-related injury. Finally, PTEN mutations/deletions or low PTEN expression are associated with diverse liver malignancies thus suggesting a critical role for PTEN in hepatic cancers. This review will focus on our current knowledge of the regulation of PTEN expression/activity and the role of this phosphatase in liver diseases.
Vinciguerra
Manlio
M
Dept. Cellular Physiology and Metabolism, Geneva Medical Faculty, Geneva, Switzerland.
Foti
Michelangelo
M
D004791:Enzyme Inhibitors / Q000494:pharmacology; D005234:Fatty Liver / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006509:Hepatitis B / Q000201:enzymology; D006526:Hepatitis C / Q000201:enzymology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008107:Liver Diseases / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D008108:Liver Diseases, Alcoholic / Q000201:enzymology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
D004791:Enzyme Inhibitors; D007328:Insulin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human