title: Oncosuppressive functions of autophagy.
abstract: Macroautophagy (herein referred to as autophagy) constitutes a phylogenetically old mechanism leading to the lysosomal degradation of cytoplasmic structures. At baseline levels, autophagy exerts homeostatic functions by ensuring the turnover of potentially harmful organelles and long-lived aggregate-prone proteins. Moreover, the autophagic flow can be dramatically upregulated in response to a plethora of stressful conditions, including glucose, amino acid, oxygen, or growth factor deprivation, accumulation of unfolded proteins in the endoplasmic reticulum, and invasion by intracellular pathogens. In some experimental settings, stress-induced autophagy has been shown to contribute to programmed cell death. Nevertheless, autophagy most often confers cytoprotection by providing cells with new metabolic substrates or by ridding them of noxious intracellular entities including protein aggregates and invading organisms. Thus, autophagy has been implicated in an ever-increasing number of human diseases including cancer. Autophagy inhibition accelerates the demise of tumor cells that are subjected to chemo- or radiotherapy, thereby constituting an interesting target for the development of anticancer strategies. However, several oncosuppressor proteins and oncoproteins have been recently shown to stimulate and inhibit the autophagic flow, respectively, suggesting that autophagy exerts bona fide tumor-suppressive functions. In this review, we will discuss the mechanisms by which autophagy may prevent oncogenesis.
authors: INSERM, U848, Villejuif, France.
authors: Eugenia
authors: E
authors: Morselli
authors: Lorenzo
authors: L
authors: Galluzzi
authors: Oliver
authors: O
authors: Kepp
authors: Guillermo
authors: G
authors: Mariño
authors: Mickael
authors: M
authors: Michaud
authors: Ilio
authors: I
authors: Vitale
authors: Maria Chiara
authors: MC
authors: Maiuri
authors: Guido
authors: G
authors: Kroemer
mesh_terms: D000818:Animals; D001343:Autophagy; D042822:Genomic Instability; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D013312:Stress, Physiological / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; D058570:TOR Serine-Threonine Kinases