title: Control of autophagy by oncogenes and tumor suppressor genes.
abstract: Multiple oncogenes (in particular phosphatidylinositol 3-kinase, PI3K; activated Akt1; antiapoptotic proteins from the Bcl-2 family) inhibit autophagy. Similarly, several tumor suppressor proteins (such as BH3-only proteins; death-associated protein kinase-1, DAPK1; the phosphatase that antagonizes PI3K, PTEN; tuberous sclerosic complex 1 and 2, TSC1 and TSC2; as well as LKB1/STK11) induce autophagy, meaning that their loss reduces autophagy. Beclin-1, which is required for autophagy induction acts as a haploinsufficient tumor suppressor protein, and other essential autophagy mediators (such as Atg4c, UVRAG and Bif-1) are bona fide oncosuppressors. One of the central tumor suppressor proteins, p53 exerts an ambiguous function in the regulation of autophagy. Within the nucleus, p53 can act as an autophagy-inducing transcription factor. Within the cytoplasm, p53 exerts a tonic autophagy-inhibitory function, and its degradation is actually required for the induction of autophagy. The role of autophagy in oncogenesis and anticancer therapy is contradictory. Chronic suppression of autophagy may stimulate oncogenesis. However, once a tumor is formed, autophagy inhibition may be a therapeutic goal for radiosensitization and chemosensitization. Altogether, the current state-of-the art suggests a complex relationship between cancer and deregulated autophagy that must be disentangled by further in-depth investigation.
authors.affiliation: INSERM, U848, Apoptosis Cancer and Immunity, F-94805 Villejuif, France.
authors.forename: M C
authors.initials: MC
authors.lastname: Maiuri
authors.forename: E
authors.initials: E
authors.lastname: Tasdemir
authors.forename: A
authors.initials: A
authors.lastname: Criollo
authors.forename: E
authors.initials: E
authors.lastname: Morselli
authors.forename: J M
authors.initials: JM
authors.lastname: Vicencio
authors.forename: R
authors.initials: R
authors.lastname: Carnuccio
authors.forename: G
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D000818:Animals; D001343:Autophagy; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D006801:Humans; D015513:Oncogene Proteins / Q000378:metabolism*; D009857:Oncogenes; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D015513:Oncogene Proteins; D025521:Tumor Suppressor Proteins