title: Autophagy-deficient mice develop multiple liver tumors.
abstract: Autophagy is a major pathway for degradation of cytoplasmic proteins and organelles, and has been implicated in tumor suppression. Here, we report that mice with systemic mosaic deletion of Atg5 and liver-specific Atg7⁻/⁻ mice develop benign liver adenomas. These tumor cells originate autophagy-deficient hepatocytes and show mitochondrial swelling, p62 accumulation, and oxidative stress and genomic damage responses. The size of the Atg7⁻/⁻ liver tumors is reduced by simultaneous deletion of p62. These results suggest that autophagy is important for the suppression of spontaneous tumorigenesis through a cell-intrinsic mechanism, particularly in the liver, and that p62 accumulation contributes to tumor progression.
authors.affiliation: Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
authors.forename: Akito
authors.initials: A
authors.lastname: Takamura
authors.forename: Masaaki
authors.initials: M
authors.lastname: Komatsu
authors.forename: Taichi
authors.initials: T
authors.lastname: Hara
authors.forename: Ayako
authors.initials: A
authors.lastname: Sakamoto
authors.forename: Chieko
authors.initials: C
authors.lastname: Kishi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Waguri
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Eishi
authors.forename: Okio
authors.initials: O
authors.lastname: Hino
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Noboru
authors.initials: N
authors.lastname: Mizushima
mesh_terms: D018248:Adenoma, Liver Cell / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D000071187:Autophagy-Related Protein 5; D000071193:Autophagy-Related Protein 7; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D008869:Microtubule-Associated Proteins / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D016133:Polymerase Chain Reaction; D051758:Transcription Factor TFIIH; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C495773:Atg5 protein, mouse; C502661:Atg7 protein, mouse; D000071187:Autophagy-Related Protein 5; C490981:Gtf2h1 protein, mouse; D008869:Microtubule-Associated Proteins; D014157:Transcription Factors; D051758:Transcription Factor TFIIH; D000071193:Autophagy-Related Protein 7