Autophagy-deficient mice develop multiple liver tumors (original) (raw)

  1. Masaaki Komatsu3,8,
  2. Taichi Hara1,9,
  3. Ayako Sakamoto3,
  4. Chieko Kishi1,
  5. Satoshi Waguri4,
  6. Yoshinobu Eishi5,
  7. Okio Hino6,
  8. Keiji Tanaka7 and
  9. Noboru Mizushima1,10
  10. 1Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113-8519, Japan;
  11. 2Department of Medicine and Rheumatology, Tokyo Medical and Dental University, Tokyo 113-8519, Japan;
  12. 3Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan;
  13. 4Department of Anatomy and Histology, Fukushima Medical University School of Medicine, Hikarigaoka, Fukushima 960-1295, Japan;
  14. 5Department of Human Pathology, Tokyo Medical and Dental University, Tokyo 113-8519, Japan;
  15. 6Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo 113-8421, Japan;
  16. 7Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan
  17. ↵8 These authors contributed equally to this work.

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.

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