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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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CK1α suppresses lung tumour growth by stabilizing PTEN and inducing autophagy
Cai, J., Li, R., Xu, X., Zhang, L., Lian, R., Fang, L., Huang, Y., Feng, X., Liu, X., Xu, L., et al. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0065-8 · Cited by 146
Lee, Y. A., Noon, L. A., Akat, K. M., Ybanez, M. D., Lee, T.-F., Berres, M.-L., Fujiwara, N., Goossens, N., Chou, H.-I., Parvin-Nejad, F. P., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-07338-z · Cited by 161
p62-mediated phase separation at the intersection of the ubiquitin-proteasome system and autophagy
Danieli, A., & Martens, S. (2018) · Journal of Cell Science · doi:10.1242/jcs.214304 · Cited by 144
“Furthermore, the finding that tissue-specific knockout of autophagy genes in mice leads to neurodegeneration or liver cancer (Hara et al., 2006; Komatsu et al., 2006; Takamura et al., 2011) and the fact that cells with defective autophagy are unable to clear certain intracellular pathogens (Randow and Youle, 2014; Der…”
BackgroundTang, G., Xu, Y., Zhang, C., Wang, N., Li, H., & Feng, Y. (2021) · Antioxidants · doi:10.3390/antiox10071076 · Cited by 150
Feedback on Fat: p62-mTORC1-Autophagy Connections
Moscat, J., & Díaz-Meco, M. T. (2011) · Cell · doi:10.1016/j.cell.2011.10.021 · Cited by 146
“Moreover, chronic increases in p62 levels cause liver cell damage, which, over time, leads to hepatocarcinogenesis (Inami et al., 2011; Takamura et al., 2011).”
BackgroundNon-oncogene Addiction to SIRT3 Plays a Critical Role in Lymphomagenesis
Li, M., Chiang, Y., Lyssiotis, C. A., Teater, M. R., Hong, J. Y., Shen, H., Wang, L., Hu, J., Jing, H., Chen, Z., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.05.002 · Cited by 143
“To test if autophagy contributes to proliferation arrest caused by SIRT3 depletion, we knocked down ATG5, which is required for formation of autophagosomes (Noda and Inagaki, 2015; Takamura et al., 2011).”
BackgroundLuo, T., Fu, J., Xu, A., Su, B., Ren, Y., Li, N., Zhu, J., Zhao, X., Dai, R., Cao, J., et al. (2015) · Autophagy · doi:10.1080/15548627.2015.1034405 · Cited by 139
“Atg7 deletion in mouse liver promotes HCC development.(4) In contrast, inhibition of ATG7 suppresses oncogenic KRASinduced breast tumor growth,(37) and high levels of ATG7 expression predict poor prognosis for breast cancer.”
Role of the transcriptional coactivators YAP/TAZ in liver cancer
Zhang, S., & Zhou, D. (2019) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2019.07.006 · Cited by 141
SCD1, autophagy and cancer: implications for therapy
Ascenzi, F., Vitis, C. D., Maugeri‐Saccà, M., Napoli, C., Ciliberto, G., & Mancini, R. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-02067-6 · Cited by 143
Role of p62/SQSTM1 in liver physiology and pathogenesis
Manley, S., Williams, J. A., & Ding, W.-X. (2013) · Experimental Biology and Medicine · doi:10.1177/1535370213489446 · Cited by 135
“Mice with specific deletion of either Atg7 or Atg5 in the liver have spontaneous development of liver adenoma, and high levels of p62 protein have been found in these mouse livers.(52,107) More importantly, Atg7/p62 DKO mice have significantly decreased liver tumourigenesis,(52) which convincingly support the notion t…”
BackgroundCalcium-dependent O-GlcNAc signaling drives liver autophagy in adaptation to starvation
Ruan, H.-B., Ma, Y., Torres, S., Zhang, B., Feriod, C., Heck, R. M., Qian, K., Fu, M., Li, X., Nathanson, M. H., et al. (2017) · Genes & Development · doi:10.1101/gad.305441.117 · Cited by 151
“…glucagon To determine the role of autophagy in liver metabolism, we generated mice deficient for hepatic Atg5, which is conjugated with Atg12 and functions in a complex with Atg16L as an E3 ubiquitin ligase that is necessary for LC3-II formation and autophagosome elongation (Takamura et al. 2011).”
BackgroundEmerging role of p62/sequestosome-1 in the pathogenesis of Alzheimer's disease
Salminen, A., Kaarniranta, K., Haapasalo, A., Hiltunen, M., Soininen, H., & Alafuzoff, I. (2012) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2011.11.005 · Cited by 153
The Relationship of Redox With Hallmarks of Cancer: The Importance of Homeostasis and Context
Xing, F., Hu, Q., Qin, Y., Xu, J., Zhang, B., Yu, X., & Wang, W. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.862743 · Cited by 142
“Liver-specific deletion of autophagy gene ATG7 was shown to cause p62 accumulation, translocation to the nucleus of Nrf2, overexpression of Nrf2-target genes, and carcinogenesis, which was prevented by p62 deficiency (117).”
BackgroundYamamoto, T., Takabatake, Y., Kimura, T., Takahashi, A., Namba, T., Matsuda, J., Minami, S., Kaimori, J.-Y., Matsui, I., Kitamura, H., et al. (2016) · Autophagy · doi:10.1080/15548627.2016.1159376 · Cited by 135
Autophagy and Cancer Metabolism
Goldsmith, J., Levine, B., & Debnath, J. (2014) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/b978-0-12-416618-9.00002-9 · Cited by 139
“Indeed, this pathway has been implicated in the spontaneous tumorigenesis of autophagy-defective liver cells (Inami et al., 2011; Takamura et al., 2011) and in the early growth acceleration of BRAF-driven lung cancers lacking Atg7 (Strohecker et al., 2013).”
BackgroundInfluentialGlioblastoma, hypoxia and autophagy: a survival-prone ‘ménage-à-trois’
Jawhari, S., Ratinaud, M., & Verdier, M. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.318 · Cited by 138
“Deletion of ATG7 has also been reported in several cancers.(80,81) In metabolic stress conditions, autophagy inhibition realized by inactivation of BECN1 or ATG5 increases DNA damage and chromosomal instabilities.”
BackgroundAutophagy and Non-Alcoholic Fatty Liver Disease
Lavallard, V., & Gual, P. (2014) · BioMed Research International · doi:10.1155/2014/120179 · Cited by 138
“Further, the expression of several autophagy related genes (atg5, Atg7, and Atg6/beclin-1) and their corresponding autophagic activity is decreased in HCC cell lines compared to normal hepatic cell lines [77, 78].”
BackgroundZhang, J. (2015) · Redox Biology · doi:10.1016/j.redox.2015.01.003 · Cited by 141
“Atg4C, Atg5, and Atg7 genetic disruptions have been found to result in tumorigenesis in mice [173,174].”
BackgroundThe PI3K, Metabolic, and Autophagy Networks: Interactive Partners in Cellular Health and Disease
Shanware, N. P., Bray, K., & Abraham, R. T. (2011) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010611-134717 · Cited by 136
EGFR-mediated autophagy in tumourigenesis and therapeutic resistance
Wu, M., & Zhang, P. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.10.030 · Cited by 126
Kinetics and protective role of autophagy in a mouse cecal ligation and puncture-induced sepsis
Takahashi, W., Watanabe, E., Fujimura, L., Watanabe‐Takano, H., Yoshidome, H., Swanson, P. E., Tokuhisa, T., Oda, S., & Hatano, M. (2013) · Critical Care · doi:10.1186/cc12839 · Cited by 133
“Thus, disturbance of autophagy in the liver could have a major impact on liver physiology and disease [41-43].”
BackgroundSchläfli, A. M., Adams, O., Galván, J. A., Gugger, M., Savic, S., Bubendorf, L., Schmid, R. A., Becker, K.-F., Tschan, M. P., Langer, R., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.9647 · Cited by 123
“Under homeostatic conditions autophagy is regarded as a tumor suppressor process, but there is evidence it is later on required for tumor progression [8, 9].”
BackgroundActivation of p62/SQSTM1–Keap1–Nuclear Factor Erythroid 2-Related Factor 2 Pathway in Cancer
Ichimura, Y., & Komatsu, M. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00210 · Cited by 132
“Intriguingly, mosaic knockouts of Atg5 or liver-specific knockouts of Atg7 in mice have demonstrated that autophagy deficiency generates benign tumors in the liver in an age-dependent manner (22, 23).”
BackgroundShi, J., Wong, J. T., Piesik, P., Fung, G., Zhang, J., Jagdeo, J. M., Li, X., Jan, E., & Luo, H. (2013) · Autophagy · doi:10.4161/auto.26059 · Cited by 125
Mitochondrial DNA: Impacting Central and Peripheral Nervous Systems
Carelli, V., & Chan, D. C. (2014) · Neuron · doi:10.1016/j.neuron.2014.11.022 · Cited by 134
“Mitochondria with degenerative morphologies have been reported to accumulate in cells when core components of the autophagy machinery are removed (Takamura et al., 2011).”
BackgroundAutophagy in tumorigenesis and cancer therapy: Dr. Jekyll or Mr. Hyde?
Zhou, S., Zhao, L., Kuang, M., Zhang, B., Liang, Z., Yi, T., Wei, Y., & Zhao, X. (2012) · Cancer Letters · doi:10.1016/j.canlet.2012.02.017 · Cited by 125
“More interestingly, Takamura and his colleagues recentlyobservedbenign liver adenomasonly in themosaicdeletion of Atg5 and liver-specific deletion of Atg7 inmouse liver [40].”
BackgroundEMT Regulation by Autophagy: A New Perspective in Glioblastoma Biology
Colella, B., Faienza, F., & Bartolomeo, S. D. (2019) · Cancers · doi:10.3390/cancers11030312 · Cited by 128
“Mice bearing systemic or tissue-specific deletion of Atg5 and Atg7 also develop tumoral masses a higher frequency than the wild type counterparts [95] and are more prone to develop cancers upon carcinogen-induced stimuli [96–98].”
BackgroundAutophagic Degradation of NBR1 Restricts Metastatic Outgrowth during Mammary Tumor Progression
Marsh, T., Kenific, C. M., Suresh, D., Velozo, H. G., Shamir, E. R., Mei, W., Tankka, A. T., Leidal, A. M., Kalavacherla, S., Woo, K., et al. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.01.025 · Cited by 124
Sun, K., Deng, W.-J., Zhang, S., Cai, N., Jiao, S., Song, J., & Wei, L. (2013) · Cell & Bioscience · doi:10.1186/2045-3701-3-35 · Cited by 123
“Liver-specific deletion of Atg7 also leads to benign liver tumors in the mice model [34].”
BackgroundRole and mechanism of autophagy‐regulating factors in tumorigenesis and drug resistance
Usman, R. M., Razzaq, F., Akbar, A., Farooqui, A. A., Iftikhar, A., Latif, A., Hassan, H., Zhao, J., Carew, J. S., Nawrocki, S. T., et al. (2020) · Asia-Pacific Journal of Clinical Oncology · doi:10.1111/ajco.13449 · Cited by 120
Calcium-permeable ion channels in control of autophagy and cancer
Kondratskyi, A. (2013) · Frontiers in Physiology · doi:10.3389/fphys.2013.00272 · Cited by 122
Tian, Y., Kuo, C.-F., Sir, D., Wang, L., Govindarajan, S., Petrovic, L. M., & Ou, J.-H. J. (2014) · Cell Death and Differentiation · doi:10.1038/cdd.2014.201 · Cited by 122
“It has been shown that the monoallelic deletion of the Beclin-1 gene in mice induced tumor lesions in various tissues,(7) Atg4C-knockout (KO) mice had increased susceptibility to carcinogens for the development of fibrosarcomas(8) and the systemic mosaic KO of Atg5 and the liver-specific KO of Atg7 in mice led to the…”
Autophagy in Human Health and Disease: Novel Therapeutic Opportunities
Giampieri, F., Afrin, S., Forbes-Hernández, T. Y., Gasparrini, M., Cianciosi, D., Reboredo‐Rodríguez, P., Varela‐López, A., Quiles, J. L., & Battino, M. A. (2018) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7234 · Cited by 117
The role of autophagy in liver cancer: Molecular mechanisms and potential therapeutic targets
Cui, J., Gong, Z., & Shen, H. (2013) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2013.02.003 · Cited by 116
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Huang, T., Song, X., Yang, Y., Wan, X., Alvarez, A. A., Sastry, N. G., Feng, H., Hu, B., & Cheng, S. (2018) · Critical Reviews™ in Oncogenesis · doi:10.1615/critrevoncog.2018027913 · Cited by 120
Diverse Functions of Autophagy in Liver Physiology and Liver Diseases
Ke, P. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20020300 · Cited by 117
“Partial suppressed tumor progression in ATG7-deficient mice liver by additional ablation of p62/SQSTM1 [511]”
BackgroundInfluentialCao, Q.-H., Liu, F., Yang, Z. L., Fu, X., Yang, Z., Liu, Q., Wang, L., Wan, X., & Fan, X. (2016) · PubMed Central · Cited by 114
At a glance: A history of autophagy and cancer
Wen, X., & Klionsky, D. J. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.11.005 · Cited by 116
“In 2011, Noboru Mizushima’s group generated autophagy-deficient mice with a systemic mosaic deletion of ATG5 or the liverspecific knockout of ATG7, both of which spontaneously accumulate benign liver adenomas [59].”
BackgroundATG5: A central autophagy regulator implicated in various human diseases
Changotra, H., Kaur, S., Yadav, S. S., Gupta, G. L., Parkash, J., & Duseja, A. K. (2022) · Cell Biochemistry and Function · doi:10.1002/cbf.3740 · Cited by 123
“Furthermore, the development of multiple benign tumors in the liver as a result of the mosaic deletion of Atg5 has been seen in the case of mice.(40) However, podocyte‐specific deletion of Atg5 results in glomerulosclerosis, p62, ubiquitin, and mitochondria accumulation in aging mice.”
Backgroundp62/SQSTM1 synergizes with autophagy for tumor growth in vivoPreprint
Wei, H., Wang, C., Croce, C. M., & Guan, J. (2014) · Genes & Development · doi:10.1101/gad.237354.113 · Cited by 120
“…been shown to play complex roles in the regulation of cancer development and progression in different stages of tumorigenesis and oncogenic events (Mathew et al. 2009; Kon et al. 2011; Lock et al. 2011; Takamura et al. 2011; Wei et al. 2011; Yang et al. 2011; Chen and Guan 2013; Choi et al. 2013).”
BackgroundResultInfluentialMolecular Pathways: Autophagy in Cancer—A Matter of Timing and Context
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“Mice with mosaicAtg5 deletion or liver-specificAtg7 deletion develop benign hepatomas (35), and Bif-1 knockout mice show increased incidence of lymphomas (36).”
BackgroundAzoulay‐Alfaguter, I., Elya, R., Avrahami, L., Katz, A., & Eldar-Finkelman, H. (2014) · Oncogene · doi:10.1038/onc.2014.390 · Cited by 114
Zhao, Y., Wang, Q., Qiu, G.-H., Zhou, S., Jing, Z., Wang, J., Wang, W., Cao, J., Han, K., Cheng, Q., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.10.011 · Cited by 116
“…the liver damage associated with lipid accumulation Cell Reports 13, 1407–1417, No in Gnb2l1Dhep mice eventually leads to spontaneous tumors (Figures S1C and S1D), similar to mice with systemic mosaic deletion of Atg5 and Atg7Dhep mice that develop benign liver adenomas (Takamura et al., 2011).”
BackgroundInfluentialIron loss triggers mitophagy through induction of mitochondrial ferritin
Hara, Y., Yanatori, I., Tanaka, A., Kishi, F., Lemasters, J. J., Nishina, S., Sasaki, K., & Hino, K. (2020) · EMBO Reports · doi:10.15252/embr.202050202 · Cited by 117
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Role of autophagy in the pathophysiology of nonalcoholic fatty liver disease: A controversial issue
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Wu, S., Lan, S., Wu, S., Chiu, Y., Lin, X., Su, I., Tsai, T., Yen, C., Lu, T., Liang, F., et al. (2018) · Hepatology · doi:10.1002/hep.29781 · Cited by 113
“Transgenic mice with mosaic deletion of autophagyrelated 5 (Atg5) or liver-specific deletion of autophagyrelated 7 (Atg7) gene only developed tumors in the liver.((13)) Similarly, in human HCC tumor tissues, decreased ATG5 and Beclin 1 (BECN1) gene expression together with SQSTM1 protein accumulation were found in com…”
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Park, C., & Cuervo, A. M. (2013) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-013-9623-7 · Cited by 118
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Manley, S., & Ding, W. (2015) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2014.12.011 · Cited by 116
p62/ SQSTM 1—Dr. Jekyll and Mr. Hyde that prevents oxidative stress but promotes liver cancer
Taniguchi, K., Yamachika, S., He, F., & Karin, M. (2016) · FEBS Letters · doi:10.1002/1873-3468.12301 · Cited by 117
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BackgroundDeregulation of UBE2C-mediated autophagy repression aggravates NSCLC progression
Guo, J., Wu, Y., Du, J., Yang, L., Chen, W., Gong, K., Dai, J., Miao, S., Jin, D., & Xi, S. (2018) · Oncogenesis · doi:10.1038/s41389-018-0054-6 · Cited by 115
Cheng, X., Ma, X., Zhu, Q., Song, D., Ding, X., Li, L., Jiang, X. M., Wang, X., Tian, R. L., Su, H., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2018.12.017 · Cited by 115
Ishisaka, A., Kawabata, K., Miki, S., Shiba, Y., Minekawa, S., Nishikawa, T., Mukai, R., Terao, J., & Kawai, Y. (2013) · PLoS ONE · doi:10.1371/journal.pone.0080843 · Cited by 115
“Autophagy is a cellular degradation-recycling system for aggregated proteins and damaged organelles, and its dysregulation characterized in Atg5 or Atg7-deifient mice is implicated in various age-related diseases including neurodegeneration [36,37], diabetes [38,39], and hepatocarcinoma [40,41].”
Autophagy Function and Regulation in Kidney Disease
Kaushal, G. P., Chandrashekar, K., Juncos, L. A., & Shah, S. V. (2020) · Biomolecules · doi:10.3390/biom10010100 · Cited by 112
“The accumulation of protein aggregates and inclusion bodies has been observed in autophagy-deficient renal tubular cells [5,6], hepatocytes [7,8], cardiomyocytes [9], and neural cells [10,11].”
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Ariosa, A., Lahiri, V., Lei, Y., Yang, Y., Yin, Z., Zhang, Z., & Klionsky, D. J. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2021.166262 · Cited by 115
An emerging role of PARK2 in cancer
Xu, L., Lin, D., Yin, D., & Koeffler, H. P. (2013) · Journal of Molecular Medicine · doi:10.1007/s00109-013-1107-0 · Cited by 114
p38 MAPK: A dual role in hepatocyte proliferation through reactive oxygen species
Tormos, A. M., Taléns‐Visconti, R., Nebreda, Á. R., & Sastre, J. (2013) · Free Radical Research · doi:10.3109/10715762.2013.821200 · Cited by 112
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Kruppa, A. J., Kishi‐Itakura, C., Masters, T. A., Rorbach, J., Grice, G. L., Kendrick‐Jones, J., Nathan, J. A., Minczuk, M. A., & Buß, F. (2018) · Developmental Cell · doi:10.1016/j.devcel.2018.01.007 · Cited by 116
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Cassidy, L. D., Young, A. R. J., Young, C. N. J., Soilleux, E. J., Fielder, E., Weigand, B. M., Lagnado, A., Brais, R., Ktistakis, N. T., Wiggins, K. A., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-14187-x · Cited by 108
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Barghout, S. H., & Schimmer, A. D. (2020) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000053 · Cited by 110
Huang, G.-M., Jiang, Q., Cai, C., Qu, M., & Shen, W. (2014) · Cancer Letters · doi:10.1016/j.canlet.2014.12.036 · Cited by 106
Autophagy and senescence in cancer therapy
Gewirtz, D. A. (2013) · Journal of Cellular Physiology · doi:10.1002/jcp.24420 · Cited by 110
Rao, R., Balusu, R., Fiskus, W. C., Mudunuru, U., Venkannagari, S., Chauhan, L., Smith, J. E., Hembruff, S. L., Ha, K., Atadja, P. W., et al. (2012) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-11-0979 · Cited by 112
Atg6 is required for multiple vesicle trafficking pathways and hematopoiesis in Drosophila
Shravage, B. V., Hill, J. H., Powers, C. M., Wu, L. P., & Baehrecke, E. H. (2013) · Development · doi:10.1242/dev.089490 · Cited by 108
Autophagy: Supporting cellular and organismal homeostasis by self-eating
Eskelinen, E. (2019) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2019.03.010 · Cited by 110
“During cancer initiation autophagy is considered anti-tumoral due to its role in protection against metabolic, oxidative and inflammatory stress (Liang et al., 1999; Qu et al., 2003; Takamura et al., 2011).”
BackgroundHMGB1 promotes ductular reaction and tumorigenesis in autophagy-deficient livers
Khambu, B., Huda, N., Chen, X., Antoine, D. J., Li, Y., Dai, G., Köhler, U. A., Zong, W., Waguri, S., Werner, S., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci91814 · Cited by 106
Role of autophagy in aging: The good, the bad, and the ugly
TABIBZADEH, S. S. (2022) · Aging Cell · doi:10.1111/acel.13753 · Cited by 107
Yang, X., Zhong, X., Tanyi, J. L., Shen, J., Xu, C., Gao, P., Zheng, T. M., DeMichele, A. M., & Zhang, L. (2013) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2012.12.083 · Cited by 105
“BECN1 and ATG5, leaded to tumor initiation [3,4,5,6], suggesting autophagy pathway has tumor suppression function.”
BackgroundThe Role of Autophagy in Hepatocellular Carcinoma
Lee, Y. J., & Jang, B. K. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms161125984 · Cited by 104
“26631 Particularly convincing evidence for the tumor-suppressive role of autophagy is the development of multiple liver adenomas in mice with a deletion of Atg5 and Atg7 [28].”
BackgroundInfluentialSirtuins' control of autophagy and mitophagy in cancer
Aventaggiato, M., Vernucci, E., Barreca, F., Russo, M. A., & Tafani, M. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107748 · Cited by 103
Circadian autophagy rhythm: a link between clock and metabolism?
Ma, D., Li, S., Molusky, M. M., & Lin, J. D. (2012) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2012.03.004 · Cited by 106
“Genetic deletion of Atg5 or Atg7 in the liver leads to the development of benign liver adenomas, likely as a result of mitochondrial dysfunction, oxidative stress, and impaired DNA damage response [86].”
BackgroundAutophagy: Detection, regulation and its role in cancer and therapy response
Hönscheid, P., Datta, K., & Muders, M. H. (2014) · International Journal of Radiation Biology · doi:10.3109/09553002.2014.907932 · Cited by 101
“In the early stages of tumor initiation and carcinogenesis, autophagy plays an important anti-carcinogenic role by clearing damaged reactive oxygen species (ROS) producing mitochondria and aberrant protein aggregates (Marino et al. 2007, Takamura et al. 2011).”
BackgroundAutophagy and Its Effects: Making Sense of Double-Edged Swords
Thorburn, A. M. (2014) · PLoS Biology · doi:10.1371/journal.pbio.1001967 · Cited by 102
“show that there may be marked differences in different tissues [25] —sometimes it’s good, sometimes not.”
BackgroundLade, A. G., Noon, L. A., & Friedman, S. L. (2013) · Current Opinion in Oncology · doi:10.1097/cco.0000000000000042 · Cited by 103
“Autophagy has been implicated in tumor suppression in liver [80].”
BackgroundPharmacological inhibitors of autophagy as novel cancer therapeutic agents
Wang, C., Hu, Q., & Shen, H. (2016) · Pharmacological Research · doi:10.1016/j.phrs.2016.01.028 · Cited by 99
Vallée, A., Lecarpentier, Y., & Vallée, J.-N. (2021) · Cancers · doi:10.3390/cancers13215557 · Cited by 101
IL-37 induces autophagy in hepatocellular carcinoma cells by inhibiting the PI3K/AKT/mTOR pathway
Li, T.-T., Zhu, D., Mou, T., Guo, Z., Pu, J., Chen, Q., Wei, X., & Wu, Z. (2017) · Molecular Immunology · doi:10.1016/j.molimm.2017.04.010 · Cited by 96
“Suppression of autophagy leads to p62 accumulation, which contributes to liver tumor formation (Takamura et al., 2011), and reduced Beclin1 levels and elevated hypoxia-inducible factor (HIF)-1α expression were associated with progression of HCC (Osman et al., 2015).”
BackgroundFilippi‐Chiela, E. C., Silva, M. M. B. E., Thomé, M. P. M., & Lenz, G. (2015) · Autophagy · doi:10.1080/15548627.2015.1009795 · Cited by 97
Nrf2 Enhances Cholangiocyte Expansion in Pten-Deficient Livers
Taguchi, K., Hirano, I., Itoh, T., Tanaka, M., Miyajima, A., Suzuki, A., Motohashi, H., & Yamamoto, M. P. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.01384-13 · Cited by 98
Induction of autophagy improves hepatic lipid metabolism in glucose-6-phosphatase deficiency
Farah, B. L., Landau, D. J., Sinha, R. A., Brooks, E. D., Wu, Y., Fung, S. Y. S., Tanaka, T., Hirayama, M., Bay, B., Koeberl, D. D., et al. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.10.008 · Cited by 99
“Interestingly, mice with tissue-specific knockout of the key autophagy gene, ATG7, also showed lipid accumulation, decreased lipid turnover, and eventual development of hepatic tumors [10,16].”
BackgroundLiu, K., Shi, Y., Guo, X., Wang, S., Ouyang, Y., Hao, M., Liu, D., Qiao, L., Li, N., Zheng, J., et al. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.276 · Cited by 99
“Further studies of mice with depletion of Atg5 or Atg7 also found that autophagy deficiency induces liver tumors.(28) In our study, we determined that transient overexpression of Beclin-1 initiates autophagy but that this autophagy does not promote apoptotic cell death.”
BackgroundMolecular signaling toward mitophagy and its physiological significance
Feng, D., Liu, L., Zhu, Y., & Chen, Q. (2013) · Experimental Cell Research · doi:10.1016/j.yexcr.2013.03.034 · Cited by 99
Rare ATG7 genetic variants predispose patients to severe fatty liver disease
Baselli, G. A., Jamialahmadi, O., Pelusi, S., Ciociola, E., Malvestiti, F., Saracino, M., Santoro, L., Cherubini, A., Dongiovanni, P., Maggioni, M., et al. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.03.031 · Cited by 97
A novel microRNAs expression signature for hepatocellular carcinoma diagnosis and prognosis
Lu, M., Kong, X., Wang, H.-G., Huang, G., Ye, C., & He, Z. (2017) · Oncotarget · doi:10.18632/oncotarget.14452 · Cited by 96
“Its deficiency is associated with a poor prognosis of HCC [21].”
BackgroundAutophagy, the innate immune response and cancer
Gerada, C., & Ryan, K. M. (2020) · Molecular Oncology · doi:10.1002/1878-0261.12774 · Cited by 99
The links between AKT and two intracellular proteolytic cascades: Ubiquitination and autophagy
Noguchi, M., Hirata, N., & Suizu, F. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2014.07.013 · Cited by 99
Nagy, P., Varga, Á., Pircs, K., Hegedűs, K., & Juhász, G. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003664 · Cited by 98
“Autophagy deficiency predisposes to cancer at least in part through accumulation of the selective autophagy cargo p62, resulting in activation of antioxidant responses and tumor formation [32].”
BackgroundHe, R., Liu, Y., Fu, W., He, X., Liu, S., Xiao, D., & Tao, Y. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02172-y · Cited by 109
Ambra1 at the crossroad between autophagy and cell death
Fimia, G. M., Corazzari, M., Antonioli, M., & Piacentini, M. (2012) · Oncogene · doi:10.1038/onc.2012.455 · Cited by 96
Risk factors for pancreatic cancer: underlying mechanisms and potential targets
Kolodecik, T. R., Shugrue, C., Ashat, M., & Thrower, E. C. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2013.00415 · Cited by 95
“…of pancreatic cancer, with reports indicating both pro-tumorigenic and tumor-suppressive roles (Liang et al., 1999; Yue et al., 2003; Levine and Kroemer, 2008; Guo et al., 2011, 2013; Takamura et al., 2011; Wei et al., 2011; Yang et al., 2011; Aghajan et al., 2012; Mah and Ryan, 2012; White, 2012).”
BackgroundChi, H., Tsai, C., Tsai, M.-M., Yeh, C., & Lin, K. (2019) · Journal of Biomedical Science · doi:10.1186/s12929-019-0517-x · Cited by 97
Autophagy in chronic liver diseases: the two faces of Janus
Gual, P., Gilgenkrantz, H., & Lotersztajn, S. (2017) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00295.2016 · Cited by 91
“The fact that mice with systemic mosaic deletion of Atg5 or liver-specific deletion of Atg7 also develop spontaneous tumors is more questionable since these tumors are benign liver adenomas (60).”
BackgroundThomas, H. E., Mercer, C. A., Carnevalli, L. S., Park, J., Andersen, J. B., Conner, E. A., Tanaka, K., Matsutani, T., Iwanami, A., Aronow, B. J., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003923 · Cited by 95
“Although a few were up-regulated in tumors, almost half were significantly down-regulated (table S4), two of which, Atg5 and Atg7, are tumor suppressors in liver (28, 29).”
Autophagy: Dual Response in the Development of Hepatocellular Carcinoma
Yazdani, H. O., Huang, H., & Tsung, A. (2019) · Cells · doi:10.3390/cells8020091 · Cited by 94
“It has been reported that p62 is necessary for the HCC initiation by maintaining metabolic homeostasis through the mTOR pathway [43] and ablation of p62 inhibits growth and proliferation [14].”
BackgroundInfluentialPrimary Cilium in Cancer Hallmarks
Fabbri, L., Bost, F., & Mazure, N. M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20061336 · Cited by 93
“Studies on autophagy-deficient mice lacking the Atg5 gene or harboring an Atg7 liver-specific deletion developed benign liver tumors, whose size was further reduced with the depletion of the ubiquitin-binding protein p62, thus indicating a suppressive role for autophagy in cell transformation [144].”
BackgroundAutophagosome biogenesis and human health
Kawabata, T., & Yoshimori, T. (2020) · Cell Discovery · doi:10.1038/s41421-020-0166-y · Cited by 102
Targeting autophagy as a potential therapeutic approach for melanoma therapy
Liu, H., He, Z., & Simon, H. (2013) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2013.06.008 · Cited by 95
“resulted in spontaneous tumor formation [41].”
Sun, K., Xu, L., Jing, Y., Han, Z., Chen, X., Cai, C., Zhao, P., Zhao, X., Yang, L., & Wei, L. (2016) · Cancer Letters · doi:10.1016/j.canlet.2016.12.004 · Cited by 93
Liu, L., He, J., Wei, X., Wan, G., Lao, Y., Xu, W., Li, Z., Hu, H., Hu, Z., Luo, X., et al. (2017) · Oncogene · doi:10.1038/onc.2017.193 · Cited by 92
Relevance of Autophagy in Parenchymal and Non-Parenchymal Liver Cells for Health and Disease
Weiskirchen, R., & Tacke, F. (2019) · Cells · doi:10.3390/cells8010016 · Cited by 91
“These tumors indeed originate from autophagy-deficient hepatocytes and are characterized by aberrant p62 protein aggregation and mitochondrial swelling as well as increased genomic damage and oxidative stress responses [8].”
BackgroundInfluential
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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