title: Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis.
abstract: Defective apoptosis renders immortalized epithelial cells highly tumorigenic, but how this is impacted by other common tumor mutations is not known. In apoptosis-defective cells, inhibition of autophagy by AKT activation or by allelic disruption of beclin1 confers sensitivity to metabolic stress by inhibiting an autophagy-dependent survival pathway. While autophagy acts to buffer metabolic stress, the combined impairment of apoptosis and autophagy promotes necrotic cell death in vitro and in vivo. Thus, inhibiting autophagy under conditions of nutrient limitation can restore cell death to apoptosis-refractory tumors, but this necrosis is associated with inflammation and accelerated tumor growth. Thus, autophagy may function in tumor suppression by mitigating metabolic stress and, in concert with apoptosis, by preventing death by necrosis.
authors.affiliation: Center for Advanced Biotechnology and Medicine, 679 Hoes Lane, Piscataway, New Jersey 08854, USA.
authors.forename: Kurt
authors.initials: K
authors.lastname: Degenhardt
authors.forename: Robin
authors.initials: R
authors.lastname: Mathew
authors.forename: Brian
authors.initials: B
authors.lastname: Beaudoin
authors.forename: Kevin
authors.initials: K
authors.lastname: Bray
authors.forename: Diana
authors.initials: D
authors.lastname: Anderson
authors.forename: Guanghua
authors.initials: G
authors.lastname: Chen
authors.forename: Chandreyee
authors.initials: C
authors.lastname: Mukherjee
authors.forename: Yufang
authors.initials: Y
authors.lastname: Shi
authors.forename: Céline
authors.initials: C
authors.lastname: Gélinas
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Fan
authors.forename: Deirdre A
authors.initials: DA
authors.lastname: Nelson
authors.forename: Shengkan
authors.initials: S
authors.lastname: Jin
authors.forename: Eileen
authors.initials: E
authors.lastname: White
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000502:physiology*; D000071186:Beclin-1; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D018450:Disease Progression; D006367:HeLa Cells; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D009336:Necrosis; D009369:Neoplasms / Q000235:genetics / Q000473:pathology* / Q000648:ultrastructure; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D052002:NF-kappa B p50 Subunit; D011506:Proteins; D051057:Proto-Oncogene Proteins c-akt