Autophagy-deficient mice develop multiple liver tumors

Akito Takamura, Masaaki Komatsu, Taichi Hara, Ayako Sakamoto, Chieko Kishi, Satoshi Waguri, Yoshinobu Eishi, Okio Hino, Keiji Tanaka, Noboru Mizushima

Research output: Contribution to journalArticle

579 Citations (Scopus)

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 cellintrinsic mechanism, particularly in the liver, and that p62 accumulation contributes to tumor progression.

Original languageEnglish
Pages (from-to)795-800
Number of pages6
JournalGenes and Development
Volume25
Issue number8
DOIs
Publication statusPublished - 2011 Apr 15
Externally publishedYes

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Autophagy
Liver
Neoplasms
Mitochondrial Swelling
Organelles
Adenoma
Proteolysis
Hepatocytes
Carcinogenesis
Oxidative Stress

Keywords

  • Autophagy
  • Model mouse
  • Oxidative stress
  • Tumorigenesis

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Takamura, A., Komatsu, M., Hara, T., Sakamoto, A., Kishi, C., Waguri, S., ... Mizushima, N. (2011). Autophagy-deficient mice develop multiple liver tumors. Genes and Development, 25(8), 795-800. https://doi.org/10.1101/gad.2016211

Autophagy-deficient mice develop multiple liver tumors. / Takamura, Akito; Komatsu, Masaaki; Hara, Taichi; Sakamoto, Ayako; Kishi, Chieko; Waguri, Satoshi; Eishi, Yoshinobu; Hino, Okio; Tanaka, Keiji; Mizushima, Noboru.

In: Genes and Development, Vol. 25, No. 8, 15.04.2011, p. 795-800.

Research output: Contribution to journalArticle

Takamura, A, Komatsu, M, Hara, T, Sakamoto, A, Kishi, C, Waguri, S, Eishi, Y, Hino, O, Tanaka, K & Mizushima, N 2011, 'Autophagy-deficient mice develop multiple liver tumors', Genes and Development, vol. 25, no. 8, pp. 795-800. https://doi.org/10.1101/gad.2016211
Takamura A, Komatsu M, Hara T, Sakamoto A, Kishi C, Waguri S et al. Autophagy-deficient mice develop multiple liver tumors. Genes and Development. 2011 Apr 15;25(8):795-800. https://doi.org/10.1101/gad.2016211
Takamura, Akito ; Komatsu, Masaaki ; Hara, Taichi ; Sakamoto, Ayako ; Kishi, Chieko ; Waguri, Satoshi ; Eishi, Yoshinobu ; Hino, Okio ; Tanaka, Keiji ; Mizushima, Noboru. / Autophagy-deficient mice develop multiple liver tumors. In: Genes and Development. 2011 ; Vol. 25, No. 8. pp. 795-800.
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