Autophagy-deficient mice develop multiple liver tumors.

By A. Takamura, M. Komatsu, Taichi Hara, A. Sakamoto, C. Kishi, S. Waguri, Y. Eishi, O. Hino, Keiji Tanaka, N. Mizushima. Genes & Development, 2011

1,308 citations recorded by the source corpus.

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.

Subfields: Cell Biology, Epidemiology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/d21ceb0fe09ec38f11e2fd202ce1f0b1084da4eb

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cell Biology

1. N. Mizushima
2. Alec C. Kimmelman
3. E. White
4. M. Komatsu
5. T. Yoshimori
6. Xiaohua Li
7. Binyun Ma
8. Shi-kun He

In Epidemiology

1. Alec C. Kimmelman
2. N. Mizushima
3. E. White
4. M. Komatsu
5. Beth Levine
6. Xiaohua Li
7. Binyun Ma
8. Shi-kun He

In Molecular Biology

1. N. Mizushima
2. Alec C. Kimmelman
3. E. White
4. M. Komatsu
5. Hozumi Motohashi
6. Xiaohua Li
7. Binyun Ma
8. Shi-kun He

Citations in the corpus

• Autophagy and Tumor Metabolism (2017, result): “In contrast, when ATG5 was completely deleted in a mosaic fashion in the whole mouse, thereby completely inhibiting autophagy in those cells with the deletion, the results were different (Takamura et al., 2011).”
• Mechanisms of Selective Autophagy (2016, neutral): “The crucial role of selective autophagy for cellular homeostasis is emphasized by the fact that tissue-specific knockout of autophagy genes in mice results in neurodegeneration or liver cancer [13 – 16].”
• Autophagy and autophagy-related proteins in cancer (2020, background): “The homozygote deletion of ATG5 predisposed to liver tumors with high penetrance mouse model [196]; the somatic point mutations of ATG5 are”
• Beclin1 Controls the Levels of p53 by Regulating the Deubiquitination Activity of USP10 and USP13 (2011, neutral): “Although autophagy deficiency has been proposed to be the mechanism for the increased tumorigenesis in BECN1+/ mice, a recent study using tissue-specific knockout mice of Atg5 and Atg7 suggests that autophagy deficiency may lead to benign tumors in livers, but not in other tissues (Takamura et al., ”
• Autophagy: Renovation of Cells and Tissues (2011, background): “, the Atg5 gene is deleted in only some populations of cells in various tissues) or with Atg7 specifically disrupted in hepatocytes (Inami et al., 2011; Takamura et al., 2011).”
• From Krebs to Clinic: Glutamine Metabolism to Cancer Therapy (2016, neutral): “BPTES inhibition of hGA(124-551), a truncated form of human kidneytype glutaminase.”
• Autophagy in malignant transformation and cancer progression (2015, neutral): “Along similar lines, ATG5 is expressed at low levels in primary melanomas as compared to benign nevi, resulting in reduced autophagic proficiency (Liu et al , 2013a), and its absence favors oncogenesis in mice (Takamura et al , 2011).”
• Phosphorylation of p62 activates the Keap1-Nrf2 pathway during selective autophagy. (2013, background): “Persistent Activation of Nrf2 through Phosphorylation of p62 in Autophagy-Deficient Liver Adenoma and Human HCC Long-term suppression of autophagy in mouse livers results in the development of multiple benign adenomas whose growth is dramatically slowed by loss of p62 (Inami et al., 2011; Takamura e”