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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenoma, Liver Cell / etiology
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Adenoma, Liver Cell / genetics
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Adenoma, Liver Cell / metabolism
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Animals
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Autophagy / genetics
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Autophagy / physiology*
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Autophagy-Related Protein 5
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Autophagy-Related Protein 7
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Immunohistochemistry
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Liver Neoplasms / etiology*
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Liver Neoplasms / genetics
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Liver Neoplasms / metabolism*
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Mice
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Mice, Mutant Strains
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Mice, Transgenic
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Microscopy, Electron
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Microtubule-Associated Proteins / genetics
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Oxidative Stress / genetics
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Oxidative Stress / physiology
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Polymerase Chain Reaction
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Transcription Factor TFIIH
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Transcription Factors / metabolism
Substances
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Atg5 protein, mouse
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Atg7 protein, mouse
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Autophagy-Related Protein 5
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Gtf2h1 protein, mouse
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Microtubule-Associated Proteins
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Transcription Factors
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Transcription Factor TFIIH
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Autophagy-Related Protein 7