Autophagy signaling and the cogwheels of cancer.
The downregulation of macroautophagy observed in cancer cells is associated with tumor progression. The regulation of macroautophagy by signaling pathways overlaps with the control of cell growth, proliferation, cell survival and death. Several tumor suppressor genes (PTEN, TSC2 and p53) involved in the mTOR signaling network have been shown to stimulate autophagy. In contrast, the oncoproteins involved in this network have the opposite effect. These findings, together with the discovery that haploinsufficiency of the tumor suppressor beclin 1 promotes tumorigenesis in various tissues in transgenic mice, give credibility to the idea that autophagy is a tumor suppressor mechanism. The induction of macroautophagy by cancer treatments may also contribute to cell eradication. However, cancer cells sometimes mobilize autophagic capacities in response to various stimuli without a fatal outcome, suggesting that they can also exploit macroautophagy for their own benefit.
Botti
Joëlle
J
INSERM U756, Faculté de Pharmacie, Université Paris-Sud, 92296 Châtenay-Malabry, France.
Djavaheri-Mergny
Mojgan
M
Pilatte
Yannick
Y
Codogno
Patrice
P
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001343:Autophagy / Q000502:physiology*; D000071186:Beclin-1; D049109:Cell Proliferation; D002470:Cell Survival; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D051379:Mice; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D009857:Oncogenes / Q000502:physiology*; D011494:Protein Kinases / Q000502:physiology; D011506:Proteins / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases
D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D011494:Protein Kinases; C546842:MTOR protein, human; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases