The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
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
Flagged first, then by citations
Research works printed but not linked: 1
- 10.1172/JCI200320039 · DOI · Paper page
Cited by
Sorted by citations
Items 301–400 of 1,000
Mitophagy in the Pathogenesis of Liver Diseases
Ke, P. (2020) · Cells · doi:10.3390/cells9040831 · Cited by 91
“The genetic ablation of ATG5 and ATG7 has been reported to spontaneously induce the development of liver cancer through the accumulation of p62/SQSTM1-driven nuclear factor erythroid-2-related factor 2 (Nrf2) and induction of antioxidant responses [450,451].”
BackgroundStress Responses from the Endoplasmic Reticulum in Cancer
Kato, H., & Nishitoh, H. (2015) · Frontiers in Oncology · doi:10.3389/fonc.2015.00093 · Cited by 95
“Defects in autophagy result in enhanced tumorigenesis, suggesting that this system plays an important role in tumor suppression (189).”
BackgroundAutophagy: A Potential Therapeutic Target of Polyphenols in Hepatocellular Carcinoma
Kiruthiga, C., Devi, K. P., Nabavi, S. M., & Bishayee, A. (2020) · Cancers · doi:10.3390/cancers12030562 · Cited by 91
Chao, X., Qian, H., Wang, S., Fulte, S., & Ding, W. (2020) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2020.0169 · Cited by 91
“Inhibition of Nrf2 may be a promising approach for treating HCC.”
BackgroundInfluentialEmerging role of the Hippo pathway in autophagy
Wang, D., He, J., Huang, B., Liu, S., Zhu, H., & Xu, T. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-03069-6 · Cited by 89
Bai, H., Inoue, J., Kawano, T., & Inazawa, J. (2012) · Oncogene · doi:10.1038/onc.2011.613 · Cited by 92
ATG4B promotes colorectal cancer growth independent of autophagic flux
Liu, P., Leung, C., Chang, Y.-H., Cheng, J., Chen, J., Weng, C.-J., Tsai, K., Hsu, C.-J., Liu, Y., Hsu, P., et al. (2014) · Autophagy · doi:10.4161/auto.29556 · Cited by 89
Mechanisms and Pathophysiological Roles of the ATG8 Conjugation Machinery
Lystad, A. H., & Simonsen, A. (2019) · Cells · doi:10.3390/cells8090973 · Cited by 89
“Conditional autophagy-deficient mouse models develop spontaneous liver tumors [196], indicating that autophagy is important for the suppression of spontaneous tumorigenesis.”
BackgroundMechanisms, pathophysiological roles and methods for analyzing mitophagy – recent insights
Williams, J. A. R., & Ding, W. (2017) · Biological Chemistry · doi:10.1515/hsz-2017-0228 · Cited by 92
“Mice with liver-specific depletion of Atg5 or Atg7 accumulate damaged mitochondria, which results in development of liver injury, steatohepatitis, and eventual adenocarcinoma (Inami et al., 2011; Takamura et al., 2011; Ni et al., 2014).”
BackgroundSun, K., Guo, X.-L., Zhao, Q.-D., Jing, Y.-Y., Kou, X.-R., Xie, X.-Q., Zhou, Y., Cai, N., Gao, L., Zhao, X., et al. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.35 · Cited by 91
You eat what you are: autophagy inhibition as a therapeutic strategy in leukemia
Sehgal, A. R., Koenig, H., Johnson, D. E., Tang, D., Amaravadi, R. K., Boyiadzis, M. M., & Lotze, M. T. (2014) · Leukemia · doi:10.1038/leu.2014.349 · Cited by 89
Matsui, T., & Fukuda, M. (2013) · EMBO Reports · doi:10.1038/embor.2013.32 · Cited by 88
“As mTORC1 activity induces translation of cell-division-related genes and inhibits programmed cell death, upregulation of mTORC1 (and/or autophagy dysfunction) is closely associated with cancer/tumour [34–36].”
Cytoprotective autophagy maintains leukemia-initiating cells in murine myeloid leukemia
Sumitomo, Y., Koya, J., Nakazaki, K., Kataoka, K., Tsuruta-Kishino, T., Morita, K., Sato, T., & Kurokawa, M. (2016) · Blood · doi:10.1182/blood-2015-12-684696 · Cited by 89
Autophagy: A challengeable paradox in cancer treatment
Ahmadi‐Dehlaghi, F., Mohammadi, P., Valipour, E., Pournaghi, P., Kiani, S., & Mansouri, K. (2023) · Cancer Medicine · doi:10.1002/cam4.5577 · Cited by 93
Kubisch, J., Türei, D., Földvári-Nagy, L., Dunai, Z. A., Zsákai, L., Varga, M., Vellai, T., Csermely, P., & Korcsmáros, T. (2013) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2013.06.009 · Cited by 87
Autophagy-deficient breast cancer shows early tumor recurrence and escape from dormancy
Aqbi, H. F., Tyutyunyk-Massey, L., Keim, R. C., Butler, S. E., Thekkudan, T., Joshi, S., Smith, T. M., Bandyopadhyay, D., Idowu, M. O., Bear, H. D., et al. (2018) · Oncotarget · doi:10.18632/oncotarget.25197 · Cited by 76
“com On the other hand, inhibition of autophagy by disruption of Beclin 1 or deletion of ATG5 increases the frequency of spontaneous malignancies [2] or liver tumor [3], respectively.”
BackgroundAutophagy at the intersection of aging, senescence, and cancer
Cassidy, L. D., & Narita, M. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13269 · Cited by 93
Zhao, P., Yin, S., Qiu, Y., Sun, C., & Yu, H. (2025) · Molecular Cancer · doi:10.1186/s12943-024-02217-2 · Cited by 102
The Role of Autophagy in Genome Stability through Suppression of Abnormal Mitosis under Starvation
Matsui, A., Kamada, Y., & Matsuura, A. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003245 · Cited by 83
“Notably, a previous study reported that compromised autophagy promotes genomic instability, such as increased DNA damage, gene amplification, and aneuploidy in mammalian cells [55], consistent with the tumor-suppressive activity of autophagy that was previously reported [56–59].”
ResultHamidi, T., Cano, C. E., Grasso, D., Garcia, M. N., Sandí, M. J., Calvo, E. L., Dagorn, J., Lomberk, G. A., Urrutia, R. A., Goruppi, S., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-0026 · Cited by 85
“Autophagy seems to be required for pancreatic cancer development (48) although, in other conditions, it can also oppose cancer progression (49, 50).”
BackgroundAutophagy in breast cancer and its implications for therapy.
Jain, K., Paranandi, K. S., Sridharan, S., & Basu, A. (2013) · PubMed Central · Cited by 84
Zhi, X., & Zhong, Q. (2015) · F1000Prime Reports · doi:10.12703/p7-18 · Cited by 83
Piperlongumine induces autophagy by targeting p38 signaling
Wang, Y., Wang, J.-W., Xiao, X., Shan, Y., Xue, B., Jiang, G., He, Q., Chen, J., Xu, H.-G., Zhao, R.-X., et al. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.358 · Cited by 83
Autophagy modulation: a prudent approach in cancer treatment?
Bishop, E., & Bradshaw, T. D. (2018) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-018-3669-6 · Cited by 87
Robertson, H., Dinkova‐Kostova, A. T., & Hayes, J. D. (2020) · Cancers · doi:10.3390/cancers12123609 · Cited by 89
Bilanges, B., Alliouachene, S., Pearce, W. P., Morelli, D., Szabadkai, G., Chung, Y.-L., Chicanne, G., Valet, C., Hill, J. M., Voshol, P. J., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01969-4 · Cited by 86
The autophagy conundrum in cancer: influence of tumorigenic metabolic reprogramming
Eng, C. H., & Abraham, R. T. (2011) · Oncogene · doi:10.1038/onc.2011.220 · Cited by 83
Ashraf, N. U., Sharma, L., Mudasir, M. A., Nazir, L. A., Umar, S. A., Sharma, P. R., Vishwakarma, R. A., & Tasduq, S. A. (2017) · Journal of Lipid Research · doi:10.1194/jlr.m077537 · Cited by 82
“autophagic flux and accumulation of SQSTM1/p62 (31).”
InfluentialMetformin mediates cardioprotection against aging‐induced ischemic necroptosis
Li, C., Mu, N., Gu, C., Liu, M., Yang, Z., Yin, Y., Chen, M., Wang, Y., Han, Y., Yu, L., et al. (2020) · Aging Cell · doi:10.1111/acel.13096 · Cited by 82
“…role in abnormal protein degradation. p62 is considered a "bridge" between autophagy and its substrates, and it is an important mediator of functional autophagic flux. p62 accumulation is believed to cause organ dysfunction, such as in the liver and brain (Hara et al., 2016; Takamura et al., 2011).”
BackgroundFlessa, C., Kyrou, I., Ansari, N. N., Kaltsas, G., Papavassiliou, A. G., Kassi, E. N., & Randeva, H. S. (2021) · Current Obesity Reports · doi:10.1007/s13679-021-00431-3 · Cited by 81
Impaired autophagy response in human hepatocellular carcinoma
Bao, L., Chandra, P. K., Moroz, K., Zhang, X., Thung, S. N., Wu, T., & Dash, S. (2013) · Experimental and Molecular Pathology · doi:10.1016/j.yexmp.2013.12.002 · Cited by 82
“Recent studies have shown that a transgenicmousewith an autophagy defect develops multiple liver tumors (Takamura et al., 2011).”
BackgroundAutophagy is a major metabolic regulator involved in cancer therapy resistance
Poillet-Perez, L., Sarry, J., & Joffre, C. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109528 · Cited by 85
Targeting autophagy in breast cancer
Maycotte, P. (2014) · World Journal of Clinical Oncology · doi:10.5306/wjco.v5.i3.224 · Cited by 84
Human apolipoprotein L1 (ApoL1) in cancer and chronic kidney disease
Hu, C. A., Klopfer, E. I., & Ray, P. E. (2012) · FEBS Letters · doi:10.1016/j.febslet.2012.03.002 · Cited by 80
“Together, these results suggest that autophagy is important for the suppression of spontaneous tumorigenesis through a cell-intrinsic mechanism in the liver, and that p62 accumulation contributes to tumor progression [70].”
BackgroundThe Evolving, Multifaceted Roles of Autophagy in Cancer
Liu, J., & Debnath, J. (2016) · Advances in cancer research · doi:10.1016/bs.acr.2016.01.005 · Cited by 82
Ke, P., & Chen, S. S.-L. (2012) · Viruses · doi:10.3390/v4102251 · Cited by 81
“In a similar fashion, mosaic depletion of ATG5 and conditional knockout of ATG7 in mice resulted in spontaneous formation of benign liver tumors [162].”
BackgroundATG7 Promotes Bladder Cancer Invasion via Autophagy‐Mediated Increased ARHGDIB mRNA Stability
Zhu, J., Tian, Z., Li, Y., Hua, X., Zhang, D., Li, J., Jin, H., Xu, J., Chen, W., Niu, B., et al. (2019) · Advanced Science · doi:10.1002/advs.201801927 · Cited by 79
Liver ASK1 protects from non‐alcoholic fatty liver disease and fibrosis
Challa, T. D., Wueest, S., Lucchini, F. C., Dedual, M. A., Modica, S., Borsigova, M., Wolfrum, C., Blüher, M., & Konrad, D. (2019) · EMBO Molecular Medicine · doi:10.15252/emmm.201810124 · Cited by 79
“Moreover, liver-specific ATG7 and ATG5-deficient mice developed multiple liver tumors due to p62 accumulation (Takamura et al , 2011).”
The evolution and ecology of benign tumors
Boutry, J., Tissot, S., Újvári, B., Capp, J., Giraudeau, M., Nedelcu, A. M., & Frédéric Thomas, A. (2021) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2021.188643 · Cited by 94
Accumulation of p62 is associated with poor prognosis in patients with triple-negative breast cancer
Yuan, Z.-Y., Luo, Li, M., Xi, S., Fu, J., & He (2013) · OncoTargets and Therapy · doi:10.2147/ott.s46222 · Cited by 84
“Autophagy deficiency enhances p62 protein levels, thereby promoting tumorigenesis and tumor progression.(22,23) In addition, the autophagy process reduces the genomic instability of cancer cells.”
Oxidative Stress and Autophagy in Cardiovascular Homeostasis
Morales, C. R., Pedrozo, Z., Lavandero, S., & Hill, J. A. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5359 · Cited by 81
“ATG5, ATG6/Beclin1, and ATG7 knockout mice, as well as ATG3-deficient T-cells, harbor increased ROS and accumulate enlarged and defective mitochondria (46, 55, 70, 71).”
Song, C., Song, C., & Tong, F. (2014) · Cytotherapy · doi:10.1016/j.jcyt.2014.04.006 · Cited by 79
Diabetes and cancer, common threads and missing links
Hua, F., Yu, J., & Hu, Z. (2016) · Cancer Letters · doi:10.1016/j.canlet.2016.02.006 · Cited by 81
Yang, A., Jiao, Y., Yang, S., Deng, M., Yang, X., Mao, C., Sun, Y., Ding, N., Li, N., Zhang, M., et al. (2018) · Cell Death and Disease · doi:10.1038/s41419-017-0216-z · Cited by 78
Autophagy in the cancer-immunity dialogue
Yamazaki, T., Pedro, J. M. B., Galluzzi, L., Kroemer, G., & Pietrocola, F. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.12.003 · Cited by 80
Gao, Z., Yi, W., Tang, J., Sun, Y., Huang, J., Lan, T., Dai, X., Xu, S., Jin, Z., & Wu, X. (2022) · International Journal of Biological Sciences · doi:10.7150/ijbs.69116 · Cited by 77
“To probe the contribution of mitophagy to UAmediated protection against APAP, we established hepatocyte-specific Atg5 haplo-insufficient mice, in which mitophagy was impaired [30].”
BackgroundKoeneke, E., Witt, O., & Oehme, I. (2015) · Cells · doi:10.3390/cells4020135 · Cited by 76
“While some studies have shown a tumor suppressive function of autophagy by knocking out genes important for autophagy induction [29–33], others have shown that the knockdown of autophagy related genes impairs autophagic flux and promotes cancer cell death in metabolically unfavorable conditions as well as in response…”
BackgroundThe post‐translational regulation of transcription factor EB (TFEB) in health and disease
Takla, M., Keshri, S., & Rubinsztein, D. C. (2023) · EMBO Reports · doi:10.15252/embr.202357574 · Cited by 77
“At the stage of gastrointestinal and hepatic tumorigenesis, cancer cell survival seems to depend, in part, on loss of function of ATGs, including ATG2B, ATG5, ATG7 (Takamura et al , 2011), ATG9B, and ATG12 (Kang et al , 2009; Frange (cid”
BackgroundThe role of autophagy in cancer: from molecular mechanism to therapeutic window
Jalali, P., Shahmoradi, A., Samii, A., Mazloomnejad, R., Hatamnejad, M. R., Saeed, A., Namdar, A., & Salehi, Z. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1528230 · Cited by 89
“In this context, mice with systemic mosaic Atg5 deletion or liver-speci fi c deletion of Atg7 spontaneously develop benign hepatic adenomas (57).”
InfluentialAutophagy—from molecular mechanisms to clinical relevance
Lippai, M., & Szatmári, Z. (2016) · Cell Biology and Toxicology · doi:10.1007/s10565-016-9374-5 · Cited by 80
Mutant p53 as a Regulator and Target of Autophagy
Shi, Y., Norberg, E., & Vakifahmetoglu-Norberg, H. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2020.607149 · Cited by 77
Autophagy in cancer cell remodeling and quality control
Hernandez, G. A., & Perera, R. M. (2022) · Molecular Cell · doi:10.1016/j.molcel.2022.03.023 · Cited by 73
Impact of context-dependent autophagy states on tumor progression
Assi, M., & Kimmelman, A. C. (2023) · Nature Cancer · doi:10.1038/s43018-023-00546-7 · Cited by 80
Metformin impairs the growth of liver kinase B1-intact cervical cancer cells
Xiao, X., He, Q., Lu, C., Werle, K. D., Zhao, R.-X., Chen, J., Davis, B. C., Cui, R., Liang, J., & Xu, Z.-X. (2012) · Gynecologic Oncology · doi:10.1016/j.ygyno.2012.06.032 · Cited by 75
“In addition to apoptosis, AMPK activation can also lead to autophagyassociated cell death [7,23,44,45].”
BackgroundYY1-MIR372-SQSTM1 regulatory axis in autophagy
Feng, L., Ma, Y., Sun, J., Shen, Q., Liu, L., Lu, H., Wang, F., Yue, Y., Li, J., Zhang, S., et al. (2014) · Autophagy · doi:10.4161/auto.29486 · Cited by 78
The Multifaceted Roles of Autophagy in Tumors—Implications for Breast Cancer
Debnath, J. (2011) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1007/s10911-011-9223-3 · Cited by 78
“Indeed, this unfortunate convergence of events has recently been implicated in the spontaneous tumorigenesis of autophagy-defective liver cells [35,103].”
Cho, J., Kim, G.-Y., Pan, C., Anduaga, J., Choi, E., Mansfield, B. C., & CHOU, J. Y. (2017) · PLoS Genetics · doi:10.1371/journal.pgen.1006819 · Cited by 75
Target acquired: Selective autophagy in cardiometabolic disease
Evans, T. D., Sergin, I., Zhang, X., & Razani, B. (2017) · Science Signaling · doi:10.1126/scisignal.aag2298 · Cited by 74
Jiménez, M. T. B., Frenis, K., Hahad, O., Steven, S., Cohen, G., Cuadrado, A., Münzel, T. F., & Daiber, A. (2022) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2022.05.016 · Cited by 77
Sharma, L., Lone, N. A., Knott, R. M., Hassan, A., & Abdullah, S. T. (2018) · Food and Chemical Toxicology · doi:10.1016/j.fct.2018.09.011 · Cited by 77
The ER stress regulator Bip mediates cadmium-induced autophagy and neuronal senescence
Wang, T., Yuan, Y., Zou, H., Yang, J., Zhao, S., Ma, Y., Wang, Y., Bian, J., Liu, X., Gu, J., et al. (2016) · Scientific Reports · doi:10.1038/srep38091 · Cited by 73
“In addition, mice with a mosaic deletion of Atg5 develop progressive deficits in motor function from neurodegeneration 68 and benign liver adenomas 69 .”
Liu, H., Zhang, L., Zhang, X., & Cui, Z. (2017) · OncoTargets and Therapy · doi:10.2147/ott.s95267 · Cited by 73
The functions of Atg8-family proteins in autophagy and cancer: linked or unrelated?
Jacquet, M., Boyer‐Guittaut, M., Fraîchard, A., & Despouy, G. (2020) · Autophagy · doi:10.1080/15548627.2020.1749367 · Cited by 72
The p53-induced Gene Ei24 Is an Essential Component of the Basal Autophagy Pathway
Zhao, Y. G., Zhao, H., Miao, L., Wang, L., Sun, F., & Zhang, H. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.415968 · Cited by 72
Han, Q., Deng, Y., Chen, S., Chen, R., Yang, M., Zhang, Z., Sun, X., Wang, W., He, Y., Wang, F., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-04994-x · Cited by 73
Challenges and Therapeutic Opportunities of Autophagy in Cancer Therapy
Silva, V. R., Neves, S. P., Santos, L. D. S., Dias, R. B., & Bezerra, D. P. (2020) · Cancers · doi:10.3390/cancers12113461 · Cited by 77
“, as mentioned above, mice with systemic mosaic deletion of atg5 and liver-specific atg7−/− develop benign liver adenomas [129].”
BackgroundPatergnani, S., Missiroli, S., Morciano, G., Perrone, M., Mantovani, C. M., Anania, G., Fiorica, F., Pinton, P., & Giorgi, C. (2021) · Cancers · doi:10.3390/cancers13225622 · Cited by 77
Autophagy, Oxidative Stress and Cancer Development
Taucher, E., Mykoliuk, I., Fediuk, M., & Smolle‐Jüttner, F. (2022) · Cancers · doi:10.3390/cancers14071637 · Cited by 75
Dong, L., He, J., Luo, L., & Wang, K. (2023) · Pharmaceuticals · doi:10.3390/ph16010092 · Cited by 80
“Mice with ATG5 homozygote deletion have a higher probability of live tumors [47].”
BackgroundThe application of nanoparticles-based ferroptosis, pyroptosis and autophagy in cancer immunotherapy
Deng, W., Shang, H., Tong, Y., Liu, X., Huang, Q., He, Y. T., Wu, J., Ba, X., Chen, Z., Chen, Y., et al. (2024) · Journal of Nanobiotechnology · doi:10.1186/s12951-024-02297-8 · Cited by 80
“Research has shown that mosaic deletion of Atg5 or Atg7 in the mouse liver leads to benign hepatomas, indicating that complete and specific autophagy deficiency can promote the initiation of liver tumors but limits their progression to malignancy [113].”
BackgroundSuppression of Autophagic Flux by Bile Acids in Hepatocytes
Manley, S., Ni, H., Kong, B., Apte, U. M., Guo, G. L., & Ding, W. (2013) · Toxicological Sciences · doi:10.1093/toxsci/kft246 · Cited by 71
“Furthermore, liver-specific Atg5 or Atg7 KO mice also have increased liver tumors but the tumor progression was significantly blunted in the Atg7/p62 double KO mice (Inami et al., 2011; Takamura et al., 2011), supporting the notion that autophagy is a bona fide tumor suppressor and increased p62 levels could be one of…”
BackgroundThe Multifaceted Roles of Autophagy in Flavivirus-Host Interactions
Ke, P. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19123940 · Cited by 78
“The gene knockout of ATGs, such as Beclin 1 and ATG5, in mice has been shown to interfere with the autophagic process and promote the development of malignant tumors [447] [448] [449] [450] [451] .”
BackgroundGlobal Analysis of Cellular Protein Flux Quantifies the Selectivity of Basal Autophagy
Zhang, T., Shen, S., Qu, J., & Ghaemmaghami, S. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.02.040 · Cited by 72
“For example, suppression of autophagy in neurons leads to extensive neurodegeneration, and liver-specific inhibition of autophagy leads to the development of hepatic adenomas (Takamura et al., 2011).”
BackgroundAutophagy in the “inflammation-carcinogenesis” pathway of liver and HCC immunotherapy
Yu, S., Wang, Y., Li, J., Claret, F. X., Li, Q., Tian, T., Liang, X., Ruan, Z., Jiang, L., Yao, Y., et al. (2017) · Cancer Letters · doi:10.1016/j.canlet.2017.09.049 · Cited by 72
Glycycoumarin ameliorates alcohol-induced hepatotoxicity via activation of Nrf2 and autophagy
Song, X., Yin, S., Huo, Y., Liang, M., Fan, L., Ye, M., & Hu, H. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.07.006 · Cited by 71
Targeting autophagy for the treatment of liver diseases
Ni, H., Williams, J. A. R., Yang, H., Shi, Y., Fan, J., & Ding, W. (2012) · Pharmacological Research · doi:10.1016/j.phrs.2012.07.003 · Cited by 72
Wible, D. J., Chao, H., Tang, D. G., & Bratton, S. B. (2019) · Cell Discovery · doi:10.1038/s41421-019-0110-1 · Cited by 70
Oxidative Stress in the Healthy and Wounded Hepatocyte: A Cellular Organelles Perspective
Mello, T., Zanieri, F., Ceni, E., & Galli, A. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/8327410 · Cited by 72
“This second line of thought is supported by the observation that, in nutrientdeprived hepatocytes, mitochondrial membrane depolarization precedes the formation of the autophagosome [127] and defective mitophagy results in accumulation of dysfunctional mitochondria, increases oxidative stress, and promotes tissue liver…”
Wang, C., Chen, S., Yeo, S., Karsli-Uzunbas, G., White, E., Mizushima, N., Virgin, H. W., & Guan, J.-L. (2016) · Journal of Cell Biology · doi:10.1083/jcb.201507023 · Cited by 69
“For example, beclin1 haplodeficiency promoted spontaneous malignancies in mouse models (lung and liver cancer, lymphomas; Liang et al., 1999; Qu et al., 2003; Yue et al., 2003), but deletion of other autophagy genes did not (Takamura et al., 2011).”
BackgroundSelf-citationChao, X., Wang, S., Fulte, S., Ma, X., Ahamed, F., Cui, W., Liu, Z., Rülicke, T., Zatloukal, K., Zong, W., et al. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2021.10.014 · Cited by 69
Crosstalk Between ROS and Autophagy in Tumorigenesis: Understanding the Multifaceted Paradox
Hasan, A., Rizvi, S. F., Parveen, S., Pathak, N., Nazir, A., & Mir, S. S. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.852424 · Cited by 77
“Other studies also demonstrated that any defect in the autophagic machinery promotes tumor initiation, including liver and breast (114, 134).”
Backgroundp62 bodies: Phase separation, NRF2 activation, and selective autophagic degradation
Komatsu, M. (2022) · IUBMB Life · doi:10.1002/iub.2689 · Cited by 69
“On the other hand, the accumulation of abnormal organelles is still observed in mouse hepatocytes with double deficiency of Atg7 and p62, as in mouse hepatocytes with Atg7-deficiency, and tumorigenesis also occurs at 12 months of age.(49) However, tumor development is markedly suppressed.”
BackgroundCui, J., Shen, H., & Lim, L. H. K. (2020) · Pharmaceuticals · doi:10.3390/ph13120432 · Cited by 72
“For instance, the systemic mosaic deletion of Atg5 and liver-specific Atg7−/− has been shown to cause benign liver adenoma development [31], while Beclin-1 haploinsufficiency induces spontaneous HCC formation [29].”
BackgroundCardiomyocyte autophagy and cancer chemotherapy
Li, D. ‘., & Hill, J. A. (2013) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2013.11.007 · Cited by 69
“Also, both hepatocyte-specific Atg7 knockout mice and mosaic Atg5deficient mice develop benign hepatic adenomas [71].”
Hepatic Fibrosis and the Microenvironment: Fertile Soil for Hepatocellular Carcinoma Development
Wallace, M. C., & Friedman, S. L. (2014) · Gene Expression · doi:10.3727/105221614x13919976902057 · Cited by 69
Chen, D., Ning, W.-R., Li, X., Yuan, W., Lao, X., Wang, J., Wu, Y., & Zheng, L. (2018) · Autophagy · doi:10.1080/15548627.2018.1474994 · Cited by 66
Regulation of Autophagy by Glycolysis in Cancer
Chu, Y., Chang, Y., Lü, W., Sheng, X., Wang, S., Xu, H., & Ma, J. (2020) · Cancer Management and Research · doi:10.2147/cmar.s279672 · Cited by 68
“For instance, deletion of ATG5 and ATG7 could develop benign liver adenomas from autophagy-deficient hepatocytes due to mitochondrial swelling and oxidative stress.(20) Autophagyrelated gene BECN1 (encoded for Beclin 1) is important in the formation of the phagophore.”
BackgroundThe Emerging Roles of Autophagy in Human Diseases
Lei, Y., & Klionsky, D. J. (2021) · Biomedicines · doi:10.3390/biomedicines9111651 · Cited by 68
Chemotherapy Resistance: Role of Mitochondrial and Autophagic Components
Bahar, E., Han, S., Kim, J., & Yoon, H. (2022) · Cancers · doi:10.3390/cancers14061462 · Cited by 67
Molecular Mechanisms of Autophagy in Cancer Development, Progression, and Therapy
Vitto, V. A. M., Bianchin, S., Zolondick, A. A., Pellielo, G., Rimessi, A., Chianese, D., Yang, H., Carbone, M., Pinton, P., Giorgi, C., et al. (2022) · Biomedicines · doi:10.3390/biomedicines10071596 · Cited by 73
An inhibition of p62/ SQSTM 1 caused autophagic cell death of several human carcinoma cells
Nihira, K., Miki, Y., Ono, K., Suzuki, T., & Sasano, H. (2014) · Cancer Science · doi:10.1111/cas.12396 · Cited by 66
Goulielmaki, M., Koustas, E., Moysidou, E., Vlassi, M., Sasazuki, T., Shirasawa, S., Zografos, G., Oikonomou, E., & Pintzas, A. (2016) · Oncotarget · doi:10.18632/oncotarget.6942 · Cited by 67
Autophagy- An emerging target for melanoma therapy
Ndoye, A., & Weeraratna, A. T. (2016) · F1000Research · doi:10.12688/f1000research.8347.1 · Cited by 73
“For example, deletion of ATG5 or ATG7 in the mouse induces spontaneous benign tumor formation in the liver and concomitant deletion of p62 reduces tumor size, implying that accumulation of p62 due to deficient autophagy contributes to tumor progression 17 .”
BackgroundLampada, A., O’Prey, J., Szabadkai, G., Ryan, K. M., Hochhauser, D., & Salomoni, P. (2017) · Cell Death and Differentiation · doi:10.1038/cdd.2017.41 · Cited by 66
Guo, B., Li, L., Guo, J., Liu, A., Wu, J., Wang, H., Shi, J., Pang, D., & Cao, Q. (2017) · Oncotarget · doi:10.18632/oncotarget.17973 · Cited by 66
“Chaperone-mediated autophagy (CMA) is a form of autophagy that prevents apoptosis [12], and can induce chemotherapy resistance by stimulating the degradation of abnormal proteins within cells and organelles and reducing the levels of reactive oxygen species [13].”
BackgroundTelomeres and Cancer: Resolving the Paradox
Nassour, J., Schmidt, T. T., & Karlseder, J. (2021) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-050420-023410 · Cited by 70
“The role for autophagy in suppressing tumor initiation is further supported by mouse genetic studies showing a considerable increase of tumor frequency when autophagy is impaired (Grishchuk et al. 2011, Qu et al. 2003, Rao et al. 2014, Takamura et al. 2011).”
BackgroundZhao, J., Hu, Y., & Peng, J. (2021) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-021-00254-z · Cited by 68
“used autophagy-deficient mice to demonstrate that direct inhibition of autophagy leads to tumorigenesis [155].”
MethodMAP4K4 mediates the SOX6-induced autophagy and reduces the chemosensitivity of cervical cancer
Huang, H., Han, Q., Han, Z., Liu, M., Shu, S., Zhang, T., Yang, X., Li, Z., Xu, Q., Guo, H., et al. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-04474-1 · Cited by 65
Reggiori, F., Komatsu, M., Finley, K. D., & Simonsen, A. (2012) · International Journal of Cell Biology · doi:10.1155/2012/156272 · Cited by 68
Autophagy and cell reprogramming
Wang, S., Xia, P., Rehm, M., & Fan, Z. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1829-3 · Cited by 66
“While autophagy reduces tumorigenesis and is associated with good prognosis in early stage cancers [62, 102, 144, 145], in advanced tumors elevated autophagy confers higher chemoresistance and tolerance to metabolic stresses [92, 96].”
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
