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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
Research works printed but not linked: 1
- 10.1172/JCI200320039 · DOI · Paper page
Cited by
Sorted by citations
Items 701–800 of 1,000
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Bestion, E., Raymond, É., Mezouar, S., & Halfon, P. (2023) · Cells · doi:10.3390/cells12131702 · Cited by 27
Roles of Stress Response in Autophagy Processes and Aging-Related Diseases
Watanabe, Y., Taguchi, K., & Tanaka, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241813804 · Cited by 29
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Hill, R. M., Fok, M., Grundy, G. J., Parsons, J. L., & Rocha, S. (2023) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2023.109951 · Cited by 30
Age-related decrease of the LAMP-2 gene expression in human leukocytes
Huang, J. A., Xu, J., Pang, S., Bai, B., & Yan, B. (2012) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2012.06.016 · Cited by 27
Gao, D., Xu, Z., Kuang, X., Qiao, P., Liu, S., Zhang, L., He, P., Jadwiga, W. S., Wang, Y., & Min, W. (2013) · Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology · doi:10.1016/j.cbpc.2013.11.004 · Cited by 26
“response, quality control of intracellular proteins and organelles, antiaging, and elimination of intracellular microbes (Takamura et al., 2011; Wirawan et al., 2012).”
BackgroundRantanen, K., Pursiheimo, J., Högel, H., Miikkulainen, P., Sundström, J. T. T., & Jaakkola, P. (2013) · Journal of Cell Science · doi:10.1242/jcs.115667 · Cited by 27
Feldman, D. E., Chen, C., Punj, V., & Machida, K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0057312 · Cited by 24
“Mice harboring a conditionally deleted Atg5 fl/fl allele [54,55] and intercrossed with Alb-cre mice were generously provided by Dr.”
MethodAutophagy is associated with cucurbitacin D-induced apoptosis in human T cell leukemia cells
Nakanishi, T., Song, Y., He, C., Wang, D., Morita, K., Tsukada, J., Kanazawa, T., & Yoshida, Y. (2016) · Medical Oncology · doi:10.1007/s12032-016-0743-y · Cited by 26
“Suppression of autophagy is involved in the growth of tumors associated with liver, breast, and ovarian cancers [5–7].”
BackgroundHoo, R. L. C., Shu, L., Cheng, K. K. Y., Wu, X., Liao, B., Wu, D., Zhou, Z., & Xu, A. (2017) · Scientific Reports · doi:10.1038/srep40657 · Cited by 26
Homeostatic Role of Autophagy in Hepatocytes
Khambu, B., Yan, S., Huda, N., Liu, G., & Yin, X. (2018) · Seminars in Liver Disease · doi:10.1055/s-0038-1669939 · Cited by 28
The Exploitation of Liposomes in the Inhibition of Autophagy to Defeat Drug Resistance
Condello, M., Mancini, G., & Meschini, S. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00787 · Cited by 26
Zhang, K., Zhang, Q., Jia, R., Xiang, S., & Xu, L. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1156383 · Cited by 25
“Studies have demonstrated that artificially inhibiting autophagy progression (through ATG5 knockout) would enhance the growth of tumors at an early stage in the liver, indicating that autophagy suppression in hepatocytes relies on tumor suppression (Takamura et al., 2011).”
BackgroundSLC7A11 in hepatocellular carcinoma: potential mechanisms, regulation, and clinical significance
Li, T.-Z. (2024) · American Journal of Cancer Research · doi:10.62347/kgcl7357 · Cited by 25
“It has been found that both mouse liver cancer models and HCC patients exhibit an imbalance in the p62-Keap1-NRF2 pathway [39, 45, 46].”
BackgroundDynamic involvement of ATG5 in cellular stress responses
Lin, H., Lin, S.-M., Chung, Y., Vonderfecht, S. L., Camden, J. M., Flodby, P., Borok, Z., Limesand, K. H., Mizushima, N., & Ann, D. K. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.428 · Cited by 28
“Mouse neonates systemic deficient for ATG5 die within a day of birth,(3) whereas mice depleted of Atg5 in selected tissues have abnormalities ranging from neurodegeneration(4) and age-related cardiomyopathy(5) to liver tumors.(6) Autophagy and senescence are two distinct, however functionally intertwined, cellular res…”
BackgroundAutophagy therapeutics: preclinical basis and initial clinical studies
Zhan, L., Li, J., & Wei, B. (2018) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-018-3688-3 · Cited by 25
Li, W., Liu, C., Huang, Z., Shi, L., Zhong, C., Zhou, W., Meng, P., Li, Z., Wang, S., Luo, F., et al. (2021) · Journal of Cell Science · doi:10.1242/jcs.255273 · Cited by 25
IGF-1 contributes to liver cancer development in diabetes patients by promoting autophagy
Shan, Y., Lu, C., Wang, J., Li, M., Ye, S., Wu, S., Huang, J., Bu, S., & Wang, F. (2022) · Annals of Hepatology · doi:10.1016/j.aohep.2022.100697 · Cited by 25
He, T., Zou, J., Sun, K., & Yang, J. (2024) · International Journal of Surgery · doi:10.1097/js9.0000000000001202 · Cited by 27
“The document by authors such as Takamura A. and Mizushima N, titled ‘ Autophagy-de fi - cient mice develop multiple liver tumors ’ [15] , established the importance of autophagy in preventing spontaneous tumor development, particularly in the liver, and highlighted the role of p62 accumulation in…”
BackgroundChang, M., Morgado, M., Warren, C. R., Hinton, C. V., Farach‐Carson, M. C., & Delk, N. A. (2013) · The Prostate · doi:10.1002/pros.22737 · Cited by 26
“Notably, knockdown of p62 in mice reduces tumor growth (19,22).”
BackgroundNovel roles of V mp1: Inhibition metastasis and proliferation of hepatocellular carcinoma
Guo, L., Yang, L., Fan, C. G., Chen, G., & Wu, F. (2012) · Cancer Science · doi:10.1111/cas.12025 · Cited by 25
Kunanopparat, A., Kimkong, I., Palaga, T., Tangkijvanich, P., Sirichindakul, B., & Hirankarn, N. (2016) · World Journal of Gastroenterology · doi:10.3748/wjg.v22.i37.8361 · Cited by 26
“Interestingly, spontaneously occurring liver tumors did not progress in chimeric mice with Atg5 or Atg7 loss [15] .”
BackgroundInfluentialMarchi, S., Bonora, M., Patergnani, S., Giorgi, C., & Pinton, P. (2016) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2016.09.080 · Cited by 25
Functional characterization of lysosomal interaction of Akt with VRK2
Hirata, N., Suizu, F., Matsuda‐Lennikov, M., Tanaka, T., Edamura, T., Ishigaki, S., Donia, T., Lithanatudom, P., Obuse, C., Iwanaga, T., et al. (2018) · Oncogene · doi:10.1038/s41388-018-0330-0 · Cited by 27
Autophagy Intertwines with Different Diseases—Recent Strategies for Therapeutic Approaches
Ramesh, J., Ronsard, L., Gao, A., & Venugopal, B. (2019) · Diseases · doi:10.3390/diseases7010015 · Cited by 26
“Takakura‘s [81] experiment on systemic mosaic Atg5 deletion or a liver-specific Atg7 deficiency mouse model with highly progressed liver benign tumors suggested that autophagy is needed for the suppression of spontaneous tumorigenesis in this model [81].”
BackgroundAutophagy inhibits TLR4‐mediated invasiveness of oral cancer cells via the NF‐κB pathway
Kong, Q., Liang, Y., He, Q., You, Y., Wu, L., Liang, L., & Liang, J. (2020) · Oral Diseases · doi:10.1111/odi.13355 · Cited by 25
Metabolic, autophagic, and mitophagic activities in cancer initiation and progression
Hjelmeland, A. B., & Zhang, J. (2016) · Biomedical Journal · doi:10.1016/j.bj.2015.10.002 · Cited by 24
“[115] Takamura A, Komatsu M, Hara T, Sakamoto A, Kishi C, Waguri S, et al.”
BackgroundAngiostatic cues from the matrix: Endothelial cell autophagy meets hyaluronan biology
Chen, C. G., & Iozzo, R. V. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.rev120.014391 · Cited by 23
Zhang, C., Yang, H., Pan, L., Zhao, G., Zhang, R., Zhang, T., Xiao, Z. J., Tong, Y., Zhang, Y., Hu, R., et al. (2021) · Cancers · doi:10.3390/cancers13051181 · Cited by 24
“Studies have found that mosaic deletion of Atg5 or liver-specific absence of Atg7 in mice led to multiple liver tumors, suggesting that autophagy plays an important role for suppressing liver tumors [16].”
BackgroundIessi, E., Vona, R., Cittadini, C., & Matarrese, P. (2021) · Biomedicines · doi:10.3390/biomedicines9121942 · Cited by 26
Kao, C.-H., Su, T.-Y., Huang, W.-S., Lu, X.-Y., Jane, W., Huang, C.-Y., Huang, H.-H., & Wang, W. (2022) · Autophagy · doi:10.1080/15548627.2022.2051880 · Cited by 25
“Studies on autophagy-deficient mice support that impaired autophagy promotes tumorigenesis [31].”
BackgroundWang, Y., Yi, Y., Yao, J., Wan, H., Yu, M., Ge, L., Zeng, X., Wu, M., & Mei, L. (2022) · Acta Biomaterialia · doi:10.1016/j.actbio.2022.09.035 · Cited by 26
Zhang, X., Zhang, M., Cui, H., Zhang, T., Wu, L., Xu, C., Yin, C., & Gao, J. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.12.032 · Cited by 25
Susceptibility of monocytes to activation correlates with atherogenic mitochondrial DNA mutations
Orekhov, A. N., Викторович, Ж. А., Kolmychkova, K. I., Mitrofanov, K., Kubekina, M. V., Ivanova, E. A., & Sobenin, I. A. (2015) · Experimental and Molecular Pathology · doi:10.1016/j.yexmp.2015.11.006 · Cited by 24
“The MT-RNR2 gene also encodes the Humanin polypeptide relevant to Alzheimer's disease research. diseases (Komatsu et al., 2006; Hara et al., 2006; Jung et al., 2008; Wu et al., 2009; Komatsu et al., 2010; Takamura et al., 2011).”
BackgroundWhat cell death does in development
Zakeri, Z., Penaloza, C. G., Smith, K., Ye, Y., & Lockshin, R. A. (2015) · The International Journal of Developmental Biology · doi:10.1387/ijdb.150220zz · Cited by 24
Xue, G., Kohler, R. S., Tang, F., Hynx, D., Wang, Y., Orso, F., Prêtre, V., Ritschard, R., Hirschmann, P., Cron, P. D., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.18213 · Cited by 25
“Nevertheless, the role of autophagy in tumor development and progression is controversial, since a range of studies has hinted at a role of autophagy in promoting apoptosis [16, 17].”
BackgroundAutophagy suppresses proliferation of HepG2 cells via inhibiting glypican-3/wnt/β-catenin signaling
Hu, P., Cheng, B., He, Y., Wei, Z., Wu, D., & Meng, Z. (2018) · OncoTargets and Therapy · doi:10.2147/ott.s150520 · Cited by 24
The many-faced role of autophagy in liver diseases
Gracia‐Sancho, J., & Guixé‐Muntet, S. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2017.09.015 · Cited by 24
Yuan, Y., Li, X., Xu, Y., Zhao, H., SU, Z., Lai, D., Yang, W., Chen, S., He, Y., Li, X., et al. (2019) · Cancer Science · doi:10.1111/cas.14192 · Cited by 24
Liu, J., Zhu, Z., Liu, Y., Wei, L., Bai, L., Mao, F., Zhang, J., Wang, Y., & Liu, Y. (2019) · Life Sciences · doi:10.1016/j.lfs.2019.117228 · Cited by 24
Lu, S., & Harrison-Findik, D. D. (2013) · World Journal of Biological Chemistry · doi:10.4331/wjbc.v4.i3.64 · Cited by 27
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Kovale, L. M., Singh, M. K., Kim, J., & Ha, J. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25168647 · Cited by 24
“…p53 is known to inhibit autophagy at basal levels, but when triggered by cellular stress like DNA damage, it activates numerous genes that promote autophagy, including DRAM1 (damage-regulated autophagy modulator 1) [59], Tsc2, and AMPK [60,61] can be regulated by certain tumor suppressive pathways.”
BackgroundKorah, J., Canaff, L., & Lebrun, J. J. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.678557 · Cited by 24
Autophagy mediates epithelial cancer chemoresistance by reducing p62/SQSTM1 accumulation
Battista, R. A., Resnati, M., Facchi, C., Ruggieri, E., Cremasco, F., Paradiso, F., Orfanelli, U., Giordano, L., Bussi, M., Cenci, S., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0201621 · Cited by 23
Yu, Y., Men, S., & Zhang, Y. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2020.107342 · Cited by 23
Novel Effects of Statins on Cancer via Autophagy
Mengual, D., Medrano, L. E., Villamizar-Villamizar, W., Osorio-Llanes, E., Mendoza‐Torres, E., & Bolívar, S. (2022) · Pharmaceuticals · doi:10.3390/ph15060648 · Cited by 26
“Evidence reveals that the monoallelic deletion of ATG7 and ATG5 leads to the development of multiple liver tumors from hepatocytes deficient in autophagy, due to damaged mitochondria and increased oxidative stress [101].”
BackgroundSmad3 Phospho-Isoform Signaling in Nonalcoholic Steatohepatitis
Yamaguchi, T., Yoshida, K., Murata, M., Suwa, K., Tsuneyama, K., Matsuzaki, K., & Naganuma, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23116270 · Cited by 25
Machida, K., Feldman, D. E., & Tsukamoto, H. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-09614-8_8 · Cited by 23
Teng, Y. (2015) · World Journal of Gastroenterology · doi:10.3748/wjg.v22.i1.300 · Cited by 26
Autophagy and mitophagy in hepatocarcinogenesis
Liu, K., Lee, J., & Ou, J. J. (2017) · Molecular & Cellular Oncology · doi:10.1080/23723556.2017.1405142 · Cited by 23
“Previous studies using mice with hepatocyte-specific knockout of Atg5 or Atg7, two genes essential for autophagy, indicated that autophagy was required to suppress the initiation of hepatocarcinogenesis.(1,2) In these mice, dysfunctional mitochondria accumulated in hepatocytes, resulting in the increase of reactive ox…”
BackgroundAydın, Y., Stephens, C. M., Chava, S. P., Heidari, Z., Panigrahi, R., Williams, D. D., Wiltz, K., Bell, A., Wilson, W., Krzysztof Reiss, F., et al. (2018) · American Journal Of Pathology · doi:10.1016/j.ajpath.2018.06.022 · Cited by 23
Complex Cell Type-Specific Roles of Autophagy in Liver Fibrosis and Cirrhosis
Hung, T., Hsiao, C.-C., Lin, C., & Lee, P. (2020) · Pathogens · doi:10.3390/pathogens9030225 · Cited by 23
“Mounting evidence indicates that alterations in the autophagic process drive the progression of various liver diseases, including α1‐antitrypsin deficiency [1–3], alcoholic and nonalcoholic fatty liver diseases [4–6], viral hepatitis B [7,8], viral hepatitis C [9,10], and hepatocellular carcinoma [8,11,12].”
BackgroundDasari, S. K., Schejter, E. D., Bialik, S., Shkedy, A., Levin‐Salomon, V., Levin‐Zaidman, S., & Kimchi, A. (2017) · Cell Cycle · doi:10.1080/15384101.2017.1380134 · Cited by 24
Aravindan, S., Ramraj, S. K., Somasundaram, S. T., & Aravindan, N. (2015) · Journal of Biomedical Science · doi:10.1186/s12929-015-0132-4 · Cited by 22
“Studies have also shown that autophagy functions as an anti-oncogenic mechanism in tumors [65-68].”
BackgroundL’autophagie : le yin et le yang des cancers
Joffre, C., Djavaheri‐Mergny, M., Pattingre, S., & Giuriato, S. (2017) · médecine/sciences · doi:10.1051/medsci/20173303021 · Cited by 24
Zhu, W., Li, J., Zhang, Y., Zhu, Z., Liu, H., Lin, Y., Hu, A., Zhou, J., Ren, H., & Shi, X. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.599124 · Cited by 22
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Zang, X., Wang, J., Xia, Y., Li, J., Chen, L., Gu, Y., & Shen, X. (2022) · Leukemia Research · doi:10.1016/j.leukres.2022.106967 · Cited by 22
Post-translational modifications of ATG8 proteins – an emerging mechanism of autophagy control
Nieto-Torres, J. L., Zaretski, S., Liu, T., Adams, P. D., & Hansen, M. (2023) · Journal of Cell Science · doi:10.1242/jcs.259725 · Cited by 23
Autophagy and microRNA dysregulation in liver diseases
Kim, K. M., & Kim, S. G. (2014) · Archives of Pharmacal Research · doi:10.1007/s12272-014-0439-9 · Cited by 22
Vij, A., Randhawa, R., Parkash, J., & Changotra, H. (2016) · Meta Gene · doi:10.1016/j.mgene.2016.07.012 · Cited by 22
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BackgroundThe Multifaceted Effects of Autophagy on the Tumor Microenvironment
Kang, R., Zeh, H. J., Lotze, M. T., & Tang, D. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-35727-6_7 · Cited by 22
The HMGB1-RAGE axis modulates the growth of autophagy-deficient hepatic tumors
Khambu, B., Hong, H., Liu, S., Liu, G., Chen, X., Dong, Z., Wan, J., & Yin, X. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-2536-7 · Cited by 22
“Our findings support the following conclusions: (1) The adenoma originates from the autophagy-deficient hepatocytes; (2) Hepatocyte-derived HMGB1 stimulates tumor cell proliferation; (3) HMGB1 mediates the proliferative signal at least in part via RAGE in a paracrine mode; and (4) Tumors developed in the presence or a…”
ResultLi, L., Liu, J., Gao, G., Zhang, K., Song, Y., & Li, H. (2020) · Cancer Medicine · doi:10.1002/cam4.3285 · Cited by 20
RetractedCharacterizing the Mechanism Behind the Progression of NAFLD to Hepatocellular Carcinoma
Nahon, P., Allaire, M., Nault, J., & Paradis, V. (2020) · Hepatic Oncology · doi:10.2217/hep-2020-0017 · Cited by 23
“At early stages, defects in hepatocellular autophagy may act as a tumor-suppression mechanism while later on, autophagy may be detrimental, supporting tumor progression and resistance to therapies [108].”
BackgroundVu, T. H., Kobayashi, M., Hegazy, A. M., Tadokoro, Y., Ueno, M., Kasahara, A., Takase, Y., Nomura, N., Peng, H. C., Ito, C., et al. (2018) · Cancer Science · doi:10.1111/cas.13695 · Cited by 21
“Unnecessary or dam- aged mitochondria are eliminated by selective autophagy, termed mitophagy, which proceeds mainly via the alternative autophagy pathway.38 PINK1/Parkin, which are frequently mutated in Parkin- son's disease (PD), are stably localized to depolarized mitochondria and initiate mitophagy, suggesting tha…”
BackgroundInfluentialA PINK1-mediated mitophagy pathway decides the fate of tumors—to be benign or malignant?
Qian, H., Chao, X., & Ding, W. (2018) · Autophagy · doi:10.1080/15548627.2018.1425057 · Cited by 22
“Mice with mosaic deletion of Atg5 or liver-specific deletion of Atg5 or Atg7 develop spontaneous benign adenoma in the livers, which is mediated by the accumulation of hepatic SQSTM1/p62 and subsequent NFE2L2/Nrf2 activation [6,7].”
BackgroundRajendran, P., Renu, K., Ali, E. M., Genena, M. A. M., Veeraraghavan, V., Sekar, R., Sekar, A. K., Tejavat, S., Barik, P., & Abdallah, B. M. (2024) · Immunity Inflammation and Disease · doi:10.1002/iid3.70041 · Cited by 29
“39,54,78,85 Furthermore, the increase of p62 enhances the stability and transcriptional activation through NRF ‐ 2 by interacting to Keap ‐ 1, which is the primary inhibitor of NRF ‐ 2.”
BackgroundAutophagy paradox: Genetic and epigenetic control of autophagy in cancer progression
Bhol, C. S., Senapati, P. K., Kar, R. K., Chew, G., Mahapatra, K. K., Lee, E. H. C., Kumar, A. P., Bhutia, S. K., & Sethi, G. (2025) · Cancer Letters · doi:10.1016/j.canlet.2025.217909 · Cited by 21
An Overview of the Perspective of Cellular Autophagy
Alharbi, Y. M., Bima, A. I. H., & Elsamanoudy, A. Z. (2021) · Journal of Microscopy and Ultrastructure · doi:10.4103/jmau.jmau_33_20 · Cited by 24
“A direct association between tumor progression and the protein level of p62/SQSTM1 of the autophagy adaptor has been reported in vivo study.[43] The accumulation of p62/SQSTM1 is induced by the suppression of autophagy which has been observed to enhance ER stress and DNA damage and to suppress kappa B nuclear factor a…”
BackgroundAutophagy and senescence, converging roles in pathophysiology as seen through mouse models
Young, A. R. J., Cassidy, L. D., & Narita, M. (2021) · Advances in cancer research · doi:10.1016/bs.acr.2021.02.001 · Cited by 22
You, B., Zhang, P., Gu, M., Yin, H., Fan, Y., Yao, H., Pan, S. Y., Xie, H., Cheng, T., Liu, H., et al. (2022) · Cancer Letters · doi:10.1016/j.canlet.2022.01.019 · Cited by 21
New perspectives on ferroptosis and its role in hepatocellular carcinoma
Cong, T., Luo, Y., Fu, Y. H. H., Liu, Y., Li, Y., & Li, X. (2022) · Chinese Medical Journal · doi:10.1097/cm9.0000000000002327 · Cited by 21
“It has been reported that an imbalance in the p62–Keap1–NRF2 pathway can be observed in both HCC patients and mouse liver cancer models.([58,59]) p62 is the key component of Mallory–Denk bodies and hyaline granules and is found in most precancerous lesions of the liver and in HCC.”
BackgroundMolecular mechanisms of autophagy and implications in liver diseases
Wu, Y., Tan, H. W. S., Lin, J.-Y., Shen, H., Wang, H., & Lu, G. X. (2023) · Liver Research · doi:10.1016/j.livres.2023.02.002 · Cited by 24
SQSTM1/p62 and Hepatic Mallory-Denk Body Formation in Alcohol-Associated Liver Disease
Qian, H., & Ding, W. (2023) · American Journal Of Pathology · doi:10.1016/j.ajpath.2023.02.015 · Cited by 22
Zhao, G., Wang, Y., Fan, Z., Xiong, J., Ertaş, Y. N., Ashammakhi, N. A., Wang, J., & Ma, T. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.216860 · Cited by 22
Nepal, S., Kim, M. J., Lee, E.-S., Kim, J., Choi, D., Sohn, D., Lee, S., Song, K., Kim, S., Jeong, G., et al. (2014) · Food and Chemical Toxicology · doi:10.1016/j.fct.2014.02.027 · Cited by 21
He, L., Ren, Y., Zheng, Q., Wang, L., Lai, Y., Guan, S., Zhang, X., Zhang, R., Wang, J., Chen, D., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.8249 · Cited by 21
“Mice with systemic deletion of ATG5 and liverspecific ATG7-/-mice were reported to develop benign liver adenomas, together with elevated cell proliferation [36].”
BackgroundLiver-directed gene therapy for murine glycogen storage disease type Ib
Kwon, J. H., Lee, Y., Cho, J., Kim, G., Anduaga, J., Starost, M. F., Mansfield, B. C., & CHOU, J. Y. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx325 · Cited by 22
Mizuno, Y., Shimada, S., Akiyama, Y., Watanabe, S., Aida, T., Ogawa, K., Ono, H., Mitsunori, Y., Ban, D., Kudo, A., et al. (2018) · Scientific Reports · doi:10.1038/s41598-017-18323-9 · Cited by 22
Nikseresht, M., Shahverdi, M., Dehghani, M., Abidi, H., Mahmoudi, R., Ghalamfarsa, G., Manzouri, L., & Ghavami, S. (2018) · Journal of Cellular Biochemistry · doi:10.1002/jcb.27467 · Cited by 21
“In another study, investigators have showed that knocking down of ATG5/ATG7 by small interfering RNA suppressed cancer cell epithelial‐mesenchymal transition (EMT) and reduced invasiveness of hepatocellular carcinoma.(60,61) An increase in expression of ATG5 may enhance sensitivity of tumor cells to anticancer drugs a…”
BackgroundDeacetylation of CHK2 by SIRT1 protects cells from oxidative stress-dependent DNA damage response
Kwon, J., Lee, S., Kim, Y.-N., & Lee, I. H. (2019) · Experimental & Molecular Medicine · doi:10.1038/s12276-019-0232-4 · Cited by 22
Nrf2 in Neoplastic and Non-Neoplastic Liver Diseases
Orrù, C., Giordano, S., & Columbano, A. (2020) · Cancers · doi:10.3390/cancers12102932 · Cited by 21
The role of autophagy in escaping therapy-induced polyploidy/senescence
Dudkowska, M., Staniak, K., Bojko, A., & Sikora, E. (2021) · Advances in cancer research · doi:10.1016/bs.acr.2021.01.004 · Cited by 21
Targeting Chaperone-Mediated Autophagy in Cancer
Thorburn, A. M., & Debnath, J. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3003390 · Cited by 21
Patra, S., Naik, P. P., Mahapatra, K. K., Alotaibi, M. R., Patil, S., Patro, B. S., Sethi, G., Efferth, T., & Bhutia, S. K. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.216843 · Cited by 20
Research Progress on the Mechanism of the Antitumor Effects of Cannabidiol
Ma, L., Liu, M., Liu, C., Zhang, H., Yang, S., An, J., Qu, G., Song, S., & Cao, Q. (2024) · Molecules · doi:10.3390/molecules29091943 · Cited by 20
“…[36] found that CBD in glioma U87-MG cells significantly interfered with and decreased the protein expression of various regulatory factors involved in the angiogenic process, such as vascular endothelial growth factor (VEGF), matrix metalloproteinase-2/9 (MMP-2/9), matrix metalloproteinase…”
BackgroundPrognostic Signature of Osteosarcoma Based on 14 Autophagy-Related Genes
Wei, Q., Yan, Q., Lv, M., Song, D., Wang, X., & Tian, K. (2021) · Pathology & Oncology Research · doi:10.3389/pore.2021.1609782 · Cited by 22
“Indeed, autophagy could contribute to suppression of tumorigenesis of liver tumor through cell-intrinsic p62 accumulation [30].”
BackgroundEmerging Role of Autophagy in the Development and Progression of Oral Squamous Cell Carcinoma
El-Aziz, Y. S. A., Leck, L. Y. W., Jansson, P. J., & Sahni, S. (2021) · Cancers · doi:10.3390/cancers13246152 · Cited by 22
Pang, Y., Lin, W., Zhan, L., Zhang, J., Zhang, S., Jin, H., Zhang, H., Wang, X., & Li, X. (2022) · Journal of Healthcare Engineering · doi:10.1155/2022/6069682 · Cited by 20
“.e synergistic effect of autologous defect and altered apoptosis activity may promote malignant differentiation of tumor, resulting in more aggressive cancer cell phenotype and poor prognosis of HCC [37].”
BackgroundRetractedZabady, S., Mahran, N. A., Soltan, M. A., Eldeen, M. A., Eid, R. A., Albogami, S. M., Fayad, E., Matboli, M., Habib, E. K., Hasanin, A. H., et al. (2022) · Current Issues in Molecular Biology · doi:10.3390/cimb44040115 · Cited by 20
“Regarding tumour progression, specifically for HCC, autophagy was largely examined for its role in fighting malignant cells by promoting apoptosis [16].”
BackgroundAutophagy, molecular chaperones, and unfolded protein response as promoters of tumor recurrence
Alhasan, B. A., Mikeladze, M. A., Guzhova, I. V., & Margulis, B. A. (2023) · Cancer and Metastasis Reviews · doi:10.1007/s10555-023-10085-3 · Cited by 20
Expression of Beclin 1 in Bladder Cancer and Its Clinical Significance
Liu, G.-H., Zhong, Q., Ye, Y., Wang, H.-B., Hu, L.-J., Qin, Z., Zeng, M., & Zeng, B.-H. (2012) · The International Journal of Biological Markers · doi:10.5301/jbm.2012.9769 · Cited by 21
Autophagy response in the liver of pigeon exposed to avermectin
Wang, X., Liu, C., Khoso, P. A., Zheng, W., Li, M., & Li, S. (2016) · Environmental Science and Pollution Research · doi:10.1007/s11356-016-6209-0 · Cited by 20
Autophagic Cell Death and Cancer Chemotherapeutics
Shimizu, S. (2015) · Springer eBooks · doi:10.1007/978-4-431-55651-0_18 · Cited by 20
Tazarotene-Induced Gene 1 Enhanced Cervical CellAutophagy through Transmembrane Protein 192
Shyu, R., Wang, C., Wu, C., Chen, M., Lee, M., Wang, L., Jiang, S., & Tsai, F. (2016) · Molecules and Cells · doi:10.14348/molcells.2016.0161 · Cited by 20
“Mice with systemic mosaic deletion of Atg5 or Atg7 develop benign liver adenomas (Takamura et al., 2011).”
A New Linkage between the Tumor Suppressor RKIP and Autophagy: Targeted Therapeutics
Wang, Y., & Bonavida, B. (2018) · Critical Reviews™ in Oncogenesis · doi:10.1615/critrevoncog.2018027211 · Cited by 19
Karampa, A. D., GOUSSIA, A. C., Glantzounis, G. K., Mastoridou, E. M., Anastasopoulos, N.-A., & Charchanti, A. V. (2022) · Cancers · doi:10.3390/cancers14030760 · Cited by 20
“Furthermore, in vivo studies in mice models with a deletion in Atg5 and Atg7, two key macroautophagy genes, have shown increased incidence for malignancies, notably only in the liver, suggesting the high sensitivity and dependence of the liver homeostasis on autophagy pathways [13,49].”
BackgroundAutophagy and hypoxia in colonic adenomas related to aggressive features
Giatromanolaki, A. N., Koukourakis, M. I., Koutsopoulos, A. V., Harris, A. L., Gatter, K. C., & Sivridis, E. (2013) · Colorectal Disease · doi:10.1111/codi.12147 · Cited by 20
Chen, P., He, Y.-H., Huang, X., Tao, S.-Q., Wang, X., YAN, H. H., Ding, K., Lobie, P. E., Wu, W., & Wu, Z. (2017) · Oncotarget · doi:10.18632/oncotarget.21080 · Cited by 20
Role of Autophagy in Cancer and Tumor Progression
Janji, B., Viry, E., Bagińska, J., Van, K. T., & Berchem, G. (2013) · InTech eBooks · doi:10.5772/55388 · Cited by 19
“Similarly, homozygote deletion of ATG5 was shown to predisposed mice specifically to liver tumors with high penetrance [12].”
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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