[PI3 kinases and the control of autophagia].
Macroautophagy or autophagy is a degradative pathway terminating in the lysosomal compartment after the formation of a cytoplasmic vacuole that engulfs macromolecules and organelles. The recent discovery of the molecular controls of autophagy that are common to eukaryotic cells from yeast to human suggests that the role of autophagy in cell functioning is far beyond its nonselective degradative capacity. The downregulation of autophagy observed in cancer cells is associated with tumor progression. The regulation of autophagy by signalling pathways overlaps with the control of cell growth, proliferation, cell survival and death. Two of these pathways play an important role in control of autophagy, the class I and III PI3K pathways. Several tumor suppressor genes (PTEN, TSC1 and 2, p53) involved in the class I PI3K mTOR signalling network have been shown to stimulate autophagy. In contrast, the oncoproteins involved in this network (Ras, class I PI3K and Akt) have the opposite effect. These findings, together with the discovery that Beclin 1, which forms a complex with the class III PI3K to initiate autophagy, is a tumor suppressor gene product give credibility of the idea that autophagy is a tumor suppressor mechanism. However, cancer cells sometimes mobilize autophagic capacities in response to various stimuli, suggesting that they can also exploit autophagy for their own benefit.
Meley
Daniel
D
Inserm U756, Signalisation et physiopathologie des cellules épithéliales, Faculté de Pharmacie, rue Jean-Baptiste-Clément, 92296 Châtenay-Malabry Cedex.
Pattingre
Sophie
S
Codogno
Patrice
P
D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D004789:Enzyme Activation; D016147:Genes, Tumor Suppressor; D006801:Humans; D009369:Neoplasms / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology*; D051059:PTEN Phosphohydrolase / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D017856:Phosphotransferases (Phosphate Group Acceptor) / Q000502:physiology; D011494:Protein Kinases / Q000502:physiology; D058570:TOR Serine-Threonine Kinases
D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D017856:Phosphotransferases (Phosphate Group Acceptor); D011494:Protein Kinases; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human; C118888:AMP-dependent kinase (ATP-forming)