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Autophagy-deficient mice develop multiple liver tumors
Open accessAbstract
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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“we also observed the accumulation of p62/SQSTM [a hallmark of defective autophagy (Klionsky et al., 2012; Mizushima et al., 2010; Takamura et al., 2011)] in the Ulk1−/− RPE indicating that the enzymatic production of LC3-II was likely due to POS induced LAP as opposed to classical autophagy.”
From Noncanonical autophagy promotes the visual cycle (2013) · cites this paper as Takamura et al., 2011
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Cites
Autophagy in the Pathogenesis of Disease
Levine, B., & Kroemer, G. (2008) · Cell · doi:10.1016/j.cell.2007.12.018 · Cited by 7,069
Autophagy fights disease through cellular self-digestion
Mizushima, N., Levine, B., Cuervo, A. M., & Klionsky, D. J. (2008) · Nature · doi:10.1038/nature06639 · Cited by 6,452
Self-citationAutophagy: process and functionPreprint
Mizushima, N. (2007) · Genes & Development · doi:10.1101/gad.1599207 · Cited by 4,104
Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice
Hara, T., Nakamura, K., Matsui, M., Yamamoto, A., Nakahara, Y., Suzuki-Migishima, R., Yokoyama, M., Mishima, K., Saito, I., Okano, H., et al. (2006) · Nature · doi:10.1038/nature04724 · Cited by 3,882
Self-citationLoss of autophagy in the central nervous system causes neurodegeneration in mice
Komatsu, M., Waguri, S., Chiba, T., Murata, S., Iwata, J.-I., Tanida, I., Ueno, T., Koike, M., Uchiyama, Y., Kominami, E., et al. (2006) · Nature · doi:10.1038/nature04723 · Cited by 3,500
Bjørkøy, G., Lamark, T., Brech, A., Outzen, H., Perander, M., Øvervatn, A., Stenmark, H., & Johansen, T. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200507002 · Cited by 3,276
The role of autophagy during the early neonatal starvation period
Kuma, A., Hatano, M., Matsui, M., Yamamoto, A., Nakaya, H., Yoshimori, T., Ohsumi, Y., Tokuhisa, T., & Mizushima, N. (2004) · Nature · doi:10.1038/nature03029 · Cited by 2,865
Self-citationImpairment of starvation-induced and constitutive autophagy in Atg7 -deficient mice
Komatsu, M., Waguri, S., Ueno, T., Iwata, J., Murata, S., Tanida, I., Ezaki, J., Mizushima, N., Ohsumi, Y., Uchiyama, Y., et al. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200412022 · Cited by 2,331
Self-citationPromotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene
Qu, X., Yu, J., Bhagat, G., Furuya, N., Hibshoosh, H., Troxel, A., Rosen, J., Eskelinen, E.-L., Mizushima, N., Ohsumi, Y., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci20039 · Cited by 2,311
Self-citationKomatsu, M., Kurokawa, H., Waguri, S., Taguchi, K., Kobayashi, A., Ichimura, Y., Sou, Y.-S., Ueno, I., Sakamoto, A., Tong, K. I., et al. (2010) · Nature Cell Biology · doi:10.1038/ncb2021 · Cited by 2,288
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Repertoires of Autophagy in the Pathogenesis of Ocular Diseases
Li, Y., Jiang, Q. L., Cao, G.-F., Yao, J., & Yan, B. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000373980 · Cited by 16,351
Autophagy: Renovation of Cells and Tissues
Mizushima, N., & Komatsu, M. (2011) · Cell · doi:10.1016/j.cell.2011.10.026 · Cited by 6,615
“, 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).”
BackgroundInfluentialAutophagy in Human Health and Disease
Choi, A. M. K., Ryter, S. W., & Levine, B. (2013) · New England Journal of Medicine · doi:10.1056/nejmra1205406 · Cited by 2,583
The Roles of PINK1, Parkin, and Mitochondrial Fidelity in Parkinson’s Disease
Pickrell, A. M., & Youle, R. J. (2015) · Neuron · doi:10.1016/j.neuron.2014.12.007 · Cited by 2,310
Oxidative stress and autophagy: The clash between damage and metabolic needs
Filomeni, G., De Zio, D., & Cecconi, F. (2015) · Cell Death & Differentiation · doi:10.1038/cdd.2014.150 · Cited by 2,195
From Krebs to clinic: glutamine metabolism to cancer therapy
Altman, B. J., Stine, Z. E., & Dang, C. V. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.71 · Cited by 2,119
“BPTES inhibition of hGA(124-551), a truncated form of human kidneytype glutaminase.”
ROS signalling in the biology of cancer
Moloney, J. N., & Cotter, T. G. (2017) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2017.05.023 · Cited by 2,030
NRF2 and the Hallmarks of Cancer
Rojo de la Vega, M., Chapman, E., & Zhang, D. D. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.03.022 · Cited by 1,672
Deconvoluting the context-dependent role for autophagy in cancer
White, E. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3262 · Cited by 1,758
Autophagy and autophagy-related proteins in cancer
Li, X., He, S., & Ma, B. (2020) · Molecular Cancer · doi:10.1186/s12943-020-1138-4 · Cited by 1,684
“The homozygote deletion of ATG5 predisposed to liver tumors with high penetrance mouse model [196]; the somatic point mutations of ATG5 are”
BackgroundAutophagy in major human diseases
Klionsky, D. J., Petroni, G., Amaravadi, R. K., Baehrecke, E. H., Ballabio, A., Boya, P., Bravo‐San Pedro, J. M., Cadwell, K., Cecconi, F., Choi, A. M. K., et al. (2021) · The EMBO Journal · doi:10.15252/embj.2021108863 · Cited by 1,585
Autophagy modulation as a potential therapeutic target for diverse diseases
Rubinsztein, D. C., Codogno, P., & Levine, B. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3802 · Cited by 1,464
Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling.
Lee, J., Giordano, S., & Zhang, J. (2012) · Biochemical Journal · doi:10.1042/bj20111451 · Cited by 1,438
Autophagy and autophagy-related pathways in cancer
Debnath, J., Gammoh, N., & Ryan, K. M. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00585-z · Cited by 1,506
Ubiquitination in disease pathogenesis and treatment
Popovic, D., Vucic, D., & Đikić, I. (2014) · Nature Medicine · doi:10.1038/nm.3739 · Cited by 1,443
From NASH to HCC: current concepts and future challenges
Anstee, Q. M., Reeves, H. L., Kotsiliti, E., Govaere, O., & Heikenwalder, M. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0145-7 · Cited by 1,392
The Cytosolic DNA-Sensing cGAS–STING Pathway in Cancer
Kwon, J., & Bakhoum, S. F. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0761 · Cited by 1,293
The role for autophagy in cancer
White, E. (2015) · Journal of Clinical Investigation · doi:10.1172/jci73941 · Cited by 1,332
“The observation that autophagy deficiency in mice results in benign hepatomas (18) suggests that autophagy may be important in liver to suppress tumor initiation, but also that autophagy may be required for progression from benign to malignant disease.”
Phosphorylation of p62 Activates the Keap1-Nrf2 Pathway during Selective Autophagy
Ichimura, Y., Waguri, S., Sou, Y., Kageyama, S., Hasegawa, J., Ishimura, R., Saito, T., Yang, Y., Kouno, T., Fukutomi, T., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.08.003 · Cited by 1,243
“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 et al., 2011).”
BackgroundAutophagy in malignant transformation and cancer progression
Galluzzi, L., Pietrocola, F., Bravo‐San Pedro, J. M., Amaravadi, R. K., Baehrecke, E. H., Cecconi, F., Codogno, P., Debnath, J., Gewirtz, D. A., Karantza, V., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201490784 · Cited by 1,182
“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).”
InfluentialMizushima, N., & Levine, B. (2020) · New England Journal of Medicine · doi:10.1056/nejmra2022774 · Cited by 1,140
P53 in survival, death and metabolic health: a lifeguard with a licence to kill.
Kruiswijk, F., Labuschagne, C. F., & Vousden, K. H. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm4007 · Cited by 1,080
Mitophagy: mechanisms, pathophysiological roles, and analysis
Ding, W.-X., & Yin, X.-M. (2012) · bchm · doi:10.1515/hsz-2012-0119 · Cited by 1,032
Autophagy—a key player in cellular and body metabolism
Kim, K. H., & Lee, M. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2014.35 · Cited by 972
The Roles of Autophagy in Cancer
Yun, C. W., & Lee, S. H. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113466 · Cited by 965
“In mice with knockout of autophagic core proteins, deletion of ATG5 and ATG7 generates liver cancers from autophagy-deficient hepatocytes due to damaged mitochondria and oxidative stress [62].”
BackgroundMetabolic control of autophagy
Galluzzi, L., Pietrocola, F., Levine, B., & Kroemer, G. (2014) · Cell · doi:10.1016/j.cell.2014.11.006 · Cited by 855
Autophagy and Tumor Metabolism
Kimmelman, A. C., & White, E. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.04.004 · Cited by 826
“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).”
ResultPharmacological modulation of autophagy: therapeutic potential and persisting obstacles
Galluzzi, L., Bravo-San Pedro, J. M., Levine, B., Green, D. R., & Kroemer, G. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.22 · Cited by 842
Beclin1 Controls the Levels of p53 by Regulating the Deubiquitination Activity of USP10 and USP13
Liu, J., Xia, H., Kim, M., Xu, L., Li, Y., Zhang, L., Cai, Y. C., Norberg, H. V., Zhang, T., Furuya, T., et al. (2011) · Cell · doi:10.1016/j.cell.2011.08.037 · Cited by 839
“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., 2011).”
Recent insights into the function of autophagy in cancerPreprint
Amaravadi, R. K., Kimmelman, A. C., & White, E. (2016) · Genes & Development · doi:10.1101/gad.287524.116 · Cited by 828
Nrf2, the Master Regulator of Anti-Oxidative Responses
Vomund, S., Schäfer, A., Parnham, M., Brüne, B., & Von Knethen, A. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18122772 · Cited by 752
“Thus, autophagy deficiency and consequent accumulation of p62/SQSTM1 is suspected to be tumorigenic [32].”
BackgroundOverexpression of Atg5 in mice activates autophagy and extends lifespan
Pyo, J.-O., Yoo, S.-M., Ahn, H.-H., Nah, J., Hong, S.-H., Kam, T.-I., Jung, S., & Jung, Y.-K. (2013) · Nature Communications · doi:10.1038/ncomms3300 · Cited by 721
p53 status determines the role of autophagy in pancreatic tumour development
Rosenfeldt, M. T., O’Prey, J., Morton, J. P., Nixon, C., MacKay, G., Mrowinska, A., Au, A., Rai, T. S., Zheng, L., Ridgway, R., et al. (2013) · Nature · doi:10.1038/nature12865 · Cited by 713
A brief history of autophagy from cell biology to physiology and disease
Mizushima, N. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0092-5 · Cited by 696
Oxidative Stress in Cancer Cell Metabolism
Arfin, S., Jha, N. K., Jha, S. K., Kesari, K. K., Ruokolainen, J., Roychoudhury, S., Rathi, B., & Kumar, D. (2021) · Antioxidants · doi:10.3390/antiox10050642 · Cited by 721
Autophagy, Metabolism, and Cancer
White, E., Mehnert, J. M., & Chan, C. S. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0490 · Cited by 689
“Mosaic loss of ATG5 in mice produces chronic liver damage, inflammation, and the development of benign liver tumors that fail toprogress to carcinoma (17).”
Persistent activation of Nrf2 through p62 in hepatocellular carcinoma cells
Inami, Y., Waguri, S., Sakamoto, A., Kouno, T., Nakada, K., Hino, O., Watanabe, S., Ando, J., Iwadate, M., Yamamoto, M. P., et al. (2011) · The Journal of Cell Biology · doi:10.1083/jcb.201102031 · Cited by 615
“How does autophagy deficiency in mouse livers cause tumorigenesis? Systemically mosaic Atg5-deficient mice show accumulation of deformed mitochondria followed by oxidative stress and genome instability in the hepatocytes, culminating in hepatocellular adenoma (Takamura et al., 2011).”
BackgroundInfluentialMechanisms of Selective Autophagy
Zaffagnini, G., & Martens, S. (2016) · Journal of Molecular Biology · doi:10.1016/j.jmb.2016.02.004 · Cited by 636
“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].”
Guo, J. Y., Karsli-Uzunbas, G., Mathew, R., Aisner, S. C., Kamphorst, J. J., Strohecker, A. M., Chen, G., Price, S., Lu, W., Teng, X., et al. (2013) · Genes & Development · doi:10.1101/gad.219642.113 · Cited by 589
“…defects promote chronic oxidative stress, tissue damage, and inflammation, the resulting genetic instability can promote cancer initiation in mouse models (Karantza-Wadsworth et al. 2007; Mathew et al. 2007; Takamura et al. 2011; White 2012), and in this context, autophagy can be tumorsuppressive.”
BackgroundThe dynamic nature of autophagy in cancerPreprint
Kimmelman, A. C. (2011) · Genes & Development · doi:10.1101/gad.17558811 · Cited by 599
“In a related fashion, the Mizushima laboratory (Takamura et al. 2011) has recently created a mouse with mosaic deletion of Atg5 in all tissues.”
BackgroundAutophagy is required for glucose homeostasis and lung tumor maintenance
Karsli-Uzunbas, G., Guo, J. Y., Price, S., Teng, X., Laddha, S. V., Khor, S., Kalaany, N. Y., Jacks, T., Chan, C. S., Rabinowitz, J. D., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0363 · Cited by 560
Dual role of autophagy in hallmarks of cancer
Singh, S. S., Vats, S., Chia, A. Y.-Q., Tan, T. Z., Deng, S., Ong, M. S., Arfuso, F., Yap, C. T., Goh, B. C., Sethi, G., et al. (2018) · Oncogene · doi:10.1038/s41388-017-0046-6 · Cited by 542
Interplay between ROS and autophagy in cancer cells, from tumor initiation to cancer therapy
Poillet-Perez, L., Despouy, G., Delage-Mourroux, R., & Boyer-Guittaut, M. (2015) · Redox Biology · doi:10.1016/j.redox.2014.12.003 · Cited by 503
Autophagy in the liver: functions in health and disease
Ueno, T., & Komatsu, M. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2016.185 · Cited by 500
Autophagy-Mediated Tumor Promotion
Guo, J. Y., Xia, B., & White, E. (2013) · Cell · doi:10.1016/j.cell.2013.11.019 · Cited by 506
“Loss of p62 reduces liver damage and hepatoma formation resulting from autophagy deficiency, indicating that aberrant accumulation of p62 is largely the cause (Komatsu et al., 2010; Takamura et al., 2011).”
BackgroundObesity, inflammation, and liver cancer
Sun, B., & Karin, M. (2011) · Journal of Hepatology · doi:10.1016/j.jhep.2011.09.020 · Cited by 507
“Curiously, disruption of autophagy, as occurs in ATG7 or ATG5 knockout mice, leads to spontaneous HCC development[146, 147].”
BackgroundAutophagy is critical for pancreatic tumor growth and progression in tumors with p53 alterations
Yang, A., Rajeshkumar, N. V., Wang, X., Yabuuchi, S., Alexander, B. M., Chu, G. C., Von Hoff, D. D., Maitra, A., & Kimmelman, A. C. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0362 · Cited by 486
“Mosaic deletion of Atg5 predisposes mice to benign liver adenomas which do not progress to malignant tumors (5).”
BackgroundChloroquine in Cancer Therapy: A Double-Edged Sword of Autophagy
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“Liver-specific Atg7-deficient mice and mice with systemic mosaic deletion of Atg5 develop benign liver adenomas (23, 24).”
BackgroundUmemura, A., He, F., Taniguchi, K., Nakagawa, H., Yamachika, S., Font-Burgada, J., Zhong, Z., Subramaniam, S., Raghunandan, S., Durán, Á., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.04.006 · Cited by 473
“Of note, whole-body p62 disruption suppresses benign adenomas in autophagy-deficient livers (Takamura et al., 2011).”
BackgroundInfluentialInside and out: the activities of senescence in cancer
Pérez-Mancera, P. A., Young, A. R. J., & Narita, M. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3773 · Cited by 462
Functions of autophagy in normal and diseased liver
Czaja, M. J., Ding, W., Donohue, T. M., Friedman, S. L., Js, K., Komatsu, M., Lemasters, J. J., Lemoine, A., Lin, J. D., Ou, J. J., et al. (2013) · Autophagy · doi:10.4161/auto.25063 · Cited by 439
Autophagy Sustains Mitochondrial Glutamine Metabolism and Growth of Braf V600E–Driven Lung Tumors
Strohecker, A. M., Guo, J. Y., Karsli-Uzunbas, G., Price, S. M., Chen, G. J., Mathew, R., McMahon, M., & White, E. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0397 · Cited by 435
“HBSS: 0 1 2 3 0 1 2 3 5078(2) #2 5078(2) #3 5079(2) #2 5079(3) #1 5125(1) #2 5125(1) #5 5311(2) #10 5317(1) #5”
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Pengo, N., Scolari, M., Oliva, L., Milan, E., Mainoldi, F., Raimondi, A., Fagioli, C., Merlini, A., Mariani, E., Pasqualetto, E., et al. (2013) · Nature Immunology · doi:10.1038/ni.2524 · Cited by 435
Kenzelmann Broz, D., Spano Mello, S., Bieging, K. T., Jiang, D., Dusek, R. L., Brady, C. A., Sidow, A., & Attardi, L. D. (2013) · Genes & Development · doi:10.1101/gad.212282.112 · Cited by 443
“…are susceptible to tumorigenesis, including Becn1 +/À mice, Atg4c À/À mice, and mice lacking Atg5 or Atg7 in the liver, which develop spontaneous tumors, chemical carcinogen-induced tumors, and benign liver tumors, respectively (Morgan and Kastan 1997; Yue et al. 2003; Takamura et al. 2011).”
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“For example, inhibition of proteasomal activity by the proteasome inhibitor and chemotherapy agent bortezomib led to an increase in the expression of autophagy genes ATG5 and ATG7, and induced autophagy.”
InfluentialAutophagy in tumour immunity and therapy
Xia, H., Green, D. R., & Zou, W. (2021) · Nature reviews. Cancer · doi:10.1038/s41568-021-00344-2 · Cited by 421
Regulation and Function of Autophagy during Cell Survival and Cell DeathPreprint
Das, G., Shravage, B. V., & Baehrecke, E. H. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008813 · Cited by 422
“Significantly, loss of Atg5 leads to benign adenomas in livers, but this phenotype is not observed in other tissues (Takamura et al. 2011).”
BackgroundObesity and cancer: inflammation bridges the two
Kolb, R. H., Sutterwala, F. S., & Zhang, W. (2016) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2016.07.005 · Cited by 431
PI3K/AKT/mTOR signaling in gastric cancer: Epigenetics and beyond
Fattahi, S., Amjadi‐Moheb, F., Tabaripour, R., Ashrafi, G. H., & Akhavan‐Niaki, H. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118513 · Cited by 408
Diverse Cellular Roles of Autophagy
Morishita, H., & Mizushima, N. (2019) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100818-125300 · Cited by 376
Self-citationMaycotte, P., & Thorburn, A. M. (2011) · Cancer Biology & Therapy · doi:10.4161/cbt.11.2.14627 · Cited by 397
Autophagy as a molecular target for cancer treatment
Kocatürk, N. M., Akkoç, Y., Kığ, C., Bayraktar, O., Gözüaçık, D., & Kutlu, Ö. (2019) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2019.04.011 · Cited by 394
Class III PI3K Vps34 plays an essential role in autophagy and in heart and liver function
Jaber, N. L., Dou, Z., Chen, J., Catanzaro, J. M., Jiang, Y.-P., Ballou, L. M., Selinger, E. S., Ouyang, X., Lin, R. Z., Zhang, J., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1112848109 · Cited by 399
Tanaka, S., Hikita, H., Tatsumi, T., Sakamori, R., Nozaki, Y., Sakane, S., Shiode, Y., Nakabori, T., Saito, Y., Hiramatsu, N., et al. (2016) · Hepatology · doi:10.1002/hep.28820 · Cited by 376
“beclin1, generates liver inflammation and tumorigenesis,((40-42)) indicating the importance of basal levels of autophagy for maintaining liver integrity.”
BackgroundAutophagy: An Essential Degradation Program for Cellular Homeostasis and Life
Chun, Y., & Kim, J. (2018) · Cells · doi:10.3390/cells7120278 · Cited by 396
“Additionally, a positive correlation between tumor progression and autophagy adaptor p62/SQSTM1 protein level was documented in vivo [208].”
BackgroundAutophagy in liver diseases: Time for translation?
Allaire, M., Rautou, P.-E., Codogno, P., & Lotersztajn, S. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2019.01.026 · Cited by 378
Autophagy in liver diseases: A review
Qian, H., Chao, X., Williams, J. A. R., Fulte, S., Li, T., Yang, L., & Ding, W. (2021) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2021.100973 · Cited by 391
Matsuzawa, Y., Hwang, S., & Cadwell, K. (2017) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042617-053253 · Cited by 384
Autophagy and disease: unanswered questions
Yang, Y., & Klionsky, D. J. (2020) · Cell Death and Differentiation · doi:10.1038/s41418-019-0480-9 · Cited by 383
Saito, T., Ichimura, Y., Taguchi, K., Suzuki, T., Mizushima, T., Takagi, K., Hirose, Y., Nagahashi, M., Iso, T., Fukutomi, T., et al. (2016) · Nature Communications · doi:10.1038/ncomms12030 · Cited by 372
“Purified Keap1 (1 mM) was pre-treated with or without the indicated compounds in pull-down assay buffer (20mM Tris-HCl (pH 7.5), 150mM NaCl, 0.5% NP-40, 0.5mM TCEP), and then 6 His-GST-Neh2(1-56) (1 mM) or 6 His-GST-Neh2(D17-51) (1 mM) was added to the mixture.”
BackgroundMethodInfluentialAutophagy and apoptosis in liver injury
Wang, K. (2015) · Cell Cycle · doi:10.1080/15384101.2015.1038685 · Cited by 366
“Autophagy through a cell-intrinsic mechanism is an important mediator for the suppression of tumorigenesis.(49) Furthermore, autophagy defect is associated with a poor prognosis of HCC.”
BackgroundAutophagy maintains tumour growth through circulating arginine
Poillet-Perez, L., Xie, X., Zhan, L., Yang, Y., Sharp, D. W., Hu, Z. S., Su, X., Maganti, A., Jiang, C., Lu, W., et al. (2018) · Nature · doi:10.1038/s41586-018-0697-7 · Cited by 363
Obesity and Cancer: The Oil that Feeds the Flame
Font-Burgada, J., Sun, B., & Karin, M. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2015.12.015 · Cited by 364
“Systemic mosaic deletion of Atg5 or liver-specific deletion of Atg7 results in liver damage and the development of benign liver adenomas (Komatsu et al., 2005; Takamura et al., 2011).”
BackgroundNoncanonical autophagy promotes the visual cycle
Kim, J.-Y., Zhao, H., Martinez, J., Doggett, T. A., Kolesnikov, A. V., Tang, P. H., Ablonczy, Z., Chan, C.-C., Zhou, Z., Green, D. R., et al. (2013) · Cell · doi:10.1016/j.cell.2013.06.012 · Cited by 347
“phagocytosis is maximal, we detected LC3-II (Figure 6A); however, we also observed the accumulation of p62/SQSTM (a hallmark of defective autophagy; Klionsky et al., 2012; Mizushima et al., 2010; Takamura et al., 2011) in the Ulk1 / RPE, indicating that the enzymatic production of LC3-II was likely due to POSinduced L…”
Gukovsky, I., Li, N., Todoric, J., Gukovskaya, A. S., & Karin, M. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.02.007 · Cited by 347
Cellular metabolic and autophagic pathways: Traffic control by redox signaling
Dodson, M. B., Darley-Usmar, V. M., & Zhang, J. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.05.014 · Cited by 333
Targeting autophagy using natural compounds for cancer prevention and therapy
Deng, S., Shanmugam, M. K., Kumar, A. P., Yap, C. T., Sethi, G., & Bishayee, A. (2019) · Cancer · doi:10.1002/cncr.31978 · Cited by 324
“leads to the formation of multiple, benign tumors developed in the liver of mice.(78) Atg7 is also involved in liver tumor development, because liver-specific knockout of Atg7 increases the rate of liver tumors in mice.”
BackgroundActivating autophagy to potentiate immunogenic chemotherapy and radiation therapy
Galluzzi, L., Bravo-San Pedro, J. M., Demaria, S., Formenti, S. C., & Kroemer, G. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.183 · Cited by 314
Khandia, R., Dadar, M., Munjal, A. K., Dhama, K., Karthik, K., Tiwari, R., Yatoo, M. I., Iqbal, H. M. N., Singh, K. P., Joshi, S. K., et al. (2019) · Cells · doi:10.3390/cells8070674 · Cited by 337
“…through inhibiting- high mobility group box 1 protein (HMGB1) Tang et al., 2010 [288] Autophagy deficiency- leads to benign hepatoma cell death Takamura et al., 2011 [291] Autophagy induced by PTEN and TSC, the tumor suppressor protein Feng et al., 2005 [301];Tsuchihara et al., 2009…”
BackgroundInfluentialTherapeutic targets in cancer cell metabolism and autophagy
Cheong, H., Lü, C., Lindsten, T., & Thompson, C. B. (2012) · Nature Biotechnology · doi:10.1038/nbt.2285 · Cited by 320
Regulation of Liver Metabolism by Autophagy
Madrigal‐Matute, J., & Cuervo, A. M. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.09.042 · Cited by 319
Hallmarks of Aging in the Liver
Hunt, N. J., Kang, S. W., Lockwood, G. P., Couteur, D. G. L., & Cogger, V. C. (2019) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2019.07.021 · Cited by 320
“Macroautophagy is the most important for maintaining hepatic homeostasis [34].”
BackgroundAutophagy and human disease: emerging themes
Schneider, J. L., & Cuervo, A. M. (2014) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2014.04.003 · Cited by 313
“Whereas primary loss of autophagy predisposes to malignant transformation [45], autophagic activation may confer tumor cells a survival advantage in metabolically stressful environments or in response to anti-oncogenic therapeutics injury [12].”
p62/SQSTM1/A170: Physiology and pathology
Komatsu, M., Kageyama, S., & Ichimura, Y. (2012) · Pharmacological Research · doi:10.1016/j.phrs.2012.07.004 · Cited by 316
Kageyama, S., Gudmundsson, S. R., Sou, Y., Ichimura, Y., Tamura, N., Kazuno, S., Ueno, T., Miura, Y., Noshiro, D., Abe, M., et al. (2021) · Nature Communications · doi:10.1038/s41467-020-20185-1 · Cited by 301
The autophagic network and cancer
Rybstein, M. D., Pedro, J. M. B., Kroemer, G., & Galluzzi, L. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0042-2 · Cited by 294
Watch What You (Self-) Eat: Autophagic Mechanisms that Modulate Metabolism
Lahiri, V., Hawkins, W. D., & Klionsky, D. J. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.03.003 · Cited by 287
“Inhibition of autophagy in mice by mosaic deletion of Atg5 or Atg7 promotes the development of liver neoplasms (Takamura et al., 2011; Inami et al., 2011).”
BackgroundAutophagy-Dependent Production of Secreted Factors Facilitates Oncogenic RAS-Driven Invasion
Lock, R., Kenific, C. M., Leidal, A. M., Salas, E., & Debnath, J. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0841 · Cited by 290
“In addition, although liver-specific deletion of ATG7 or ATG5 initiates the development of benign adenomas, these tumors are unable to progress to adenocarcinomas, suggesting that autophagy is required for advanced tumor progression (42, 43).”
p62/SQSTM1 – steering the cell through health and disease
Sánchez‐Martín, P., & Komatsu, M. (2018) · Journal of Cell Science · doi:10.1242/jcs.222836 · Cited by 289
“A physiological problem arises with this non-canonical mechanism, referred to as the SQSTM1-mediated Keap1–Nrf2 pathway, when autophagy is defective, as accumulation of SQSTM1 leads to persistent activation of Nrf2, which causes tissue damage and tumorigenesis in liver of hepatocyte-specific Atg7-knockout mice (Ichimu…”
BackgroundThe Upstream Pathway of mTOR-Mediated Autophagy in Liver Diseases
Wang, H., Liu, Y., Wang, D., Xu, Y., Dong, R., Yang, Y., Lv, Q., Chen, X., & Zhang, Z. (2019) · Cells · doi:10.3390/cells8121597 · Cited by 286
Role and Mechanisms of Mitophagy in Liver Diseases
Ma, X., McKeen, T., Zhang, J., & Ding, W. (2020) · Cells · doi:10.3390/cells9040837 · Cited by 288
“Subsequent findings from mice with liver-specific deletion of either Atg5 or Atg7 show spontaneous liver tumors, unequivocally indicating that autophagy is a bona fide tumor suppressor [196,197].”
BackgroundEmerging strategies to effectively target autophagy in cancer
Rebecca, V. W., & Amaravadi, R. K. (2015) · Oncogene · doi:10.1038/onc.2015.99 · Cited by 290
Dynamic regulation of macroautophagy by distinctive ubiquitin-like proteins
Klionsky, D. J., & Schulman, B. A. (2014) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2787 · Cited by 284
Nrf2 promotes the development of fibrosis and tumorigenesis in mice with defective hepatic autophagy
Ni, H.-M., Woolbright, B. L., Williams, J., Copple, B., Cui, W., Luyendyk, J. P., Jaeschke, H., & Ding, W.-X. (2014) · Journal of Hepatology · doi:10.1016/j.jhep.2014.04.043 · Cited by 270
“Previous studies, including ours, showed that loss of autophagy in livers caused persistent activation of Nrf2 by activating the noncanonical p62-Keap1-Nrf2 pathway [2, 13, 15].”
InfluentialRole of tumor and host autophagy in cancer metabolismPreprint
Poillet-Perez, L., & White, E. (2019) · Genes & Development · doi:10.1101/gad.325514.119 · Cited by 273
“In tissues such as the pancreas and liver, where tumor initiation is caused by chronic tissue damage and inflammation, ablation of Atg7 or Atg5 leads to induction of benign pancreatic intraepithelial neoplasia (PANIN) in Kras mice and spontaneous liver adenomas, respectively, that fail to progress to malignancy (Takam…”
BackgroundAutophagy: shaping the tumor microenvironment and therapeutic response
Maes, H., Rubio, N., Garg, A. D., & Agostinis, P. (2013) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2013.04.005 · Cited by 272
Jiao, L., Zhang, H., Li, D., Yang, K.-L., Tang, J., Li, X., Ji, J., Yu, Y., Wu, R.-Y., Senthilkumar, R., et al. (2017) · Autophagy · doi:10.1080/15548627.2017.1381804 · Cited by 267
“liver-specific deletion of either the Atg5 or Atg7 gene in mice results in benign liver adenomas [6].”
BackgroundAutophagy and organelle homeostasis in cancer
Miller, D. R., & Thorburn, A. M. (2021) · Developmental Cell · doi:10.1016/j.devcel.2021.02.010 · Cited by 271
Cianfanelli, V., Fuoco, C., Lorente, M., Salazar‐Roa, M., Quondamatteo, F., Gherardini, P. F., Zio, D. D., Nazio, F., Antonioli, M., D’Orazio, M., et al. (2014) · Nature Cell Biology · doi:10.1038/ncb3072 · Cited by 267
“First, autophagy represents a preventive mechanism against the accumulation of damaged organelles and genome, so counteracting tumour formation.35–38 Second, autophagy supplies fuel essential for established tumour growth.45–47 Considering AMBRA1’s place in the cascade of events leading to…”
Therapeutic Targeting of Autophagy in Disease: Biology and Pharmacology
Cheng, Y., Ren, X., Hait, W. N., & Yang, J. (2013) · Pharmacological Reviews · doi:10.1124/pr.112.007120 · Cited by 262
“Mice with a systemic mosaic deletion of Atg5 or mice with a liver-specific Atg7 deficiency developed benign tumors in the liver, suggesting that autophagy is critical for suppression of spontaneous tumorigenesis in this model (Takamura et al., 2011).”
Background
Metadata
- Authors
- Takamura, A., Komatsu, M., Hara, T., Sakamoto, A., Kishi, C., Waguri, S., Eishi, Y., Hino, O., Tanaka, K., & Mizushima, N.
- Affiliations
- Tokyo Medical and Dental University (JP)
- Tokyo Metropolitan Institute of Medical Science (JP)
- Fukushima Medical University (JP)
- Juntendo University (JP)
- ORCID
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2011-04-15
- Volume
- 25
- Issue
- 8
- Pages
- 795-800
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC3078705
- OpenAlex
- W2116836791
- Cited by
- 1,342
- References
- 39
- Citations by year
- 2026: 34 · 2025: 68 · 2024: 87 · 2023: 66 · 2022: 110 · 2021: 129 · 2020: 108 · 2019: 120 · 2018: 93 · 2017: 80 · 2016: 95 · 2015: 77 · 2014: 85 · 2013: 106 · 2012: 57
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (21659045, 21000012)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- autophagy, liver tumors, ATG5, ATG7, p62, tumor suppression, mitochondrial swelling, oxidative stress, genomic damage, spontaneous tumor development, hepatocytes
- MeSH terms
- Autophagy-Related Protein 5, Autophagy-Related Protein 7, Animals, Autophagy, Immunohistochemistry, Liver Neoplasms, Mice, Mutant Strains, Mice, Transgenic, Microscopy, Electron, Microtubule-Associated Proteins, Transcription Factors, Polymerase Chain Reaction, Adenoma, Liver Cell, Oxidative Stress, Mice, Transcription Factor TFIIH
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