The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
ER Stress Cooperates with Hypernutrition to Trigger TNF-Dependent Spontaneous HCC Development
Open accessAbstract
Endoplasmic reticulum (ER) stress has been implicated in the pathogenesis of viral hepatitis, insulin resistance, hepatosteatosis, and nonalcoholic steatohepatitis (NASH), disorders that increase risk of hepatocellular carcinoma (HCC). To determine whether and how ER stress contributes to obesity-driven hepatic tumorigenesis we fed wild-type (WT) and MUP-uPA mice, in which hepatocyte ER stress is induced by plasminogen activator expression, with high-fat diet. Although both strains were equally insulin resistant, the MUP-uPA mice exhibited more liver damage, more immune infiltration, and increased lipogenesis and, as a result, displayed classical NASH signs and developed typical steatohepatitic HCC. Both NASH and HCC development were dependent on TNF produced by inflammatory macrophages that accumulate in the MUP-uPA liver in response to hepatocyte ER stress.
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“Several transgenic animals have been developed to study MASH pathogenesis, including those that overexpress urokinase-type plasminogen activator (MUP-uPA) (221) or sterol regulatory element-binding protein 1 (SREBP1) (222, 223).”
From Found in translation—Fibrosis in metabolic dysfunction–associated steatohepatitis (MASH) (2023) · cites this paper as [221]
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Cites
Steatohepatitis: A tale of two “hits”?
Day, C. P., & James, O. F. W. (1998) · Gastroenterology · doi:10.1016/s0016-5085(98)70599-2 · Cited by 4,285
El-Serag, H. B. (2011) · New England Journal of Medicine · doi:10.1056/nejmra1001683 · Cited by 3,529
Endoplasmic reticulum stress and the inflammatory basis of metabolic disease
Hotamisligil, G. S. (2010) · Cell · doi:10.1016/j.cell.2010.02.034 · Cited by 2,802
Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis
Tilg, H., & Moschen, A. R. (2010) · Hepatology · doi:10.1002/hep.24001 · Cited by 2,548
Özcan, U., Yilmaz, E., Özcan, L., Furuhashi, M., Vaillancourt, E., Smith, R. O., Görgün, C. Z., & Hotamisligil, G. S. (2006) · Science · doi:10.1126/science.1128294 · Cited by 2,413
Endoplasmic reticulum stress: cell life and death decisions
Xu, C. (2005) · Journal of Clinical Investigation · doi:10.1172/jci26373 · Cited by 2,291
Human Fatty Liver Disease: Old Questions and New Insights
Cohen, J. C., Horton, J. D., & Hobbs, H. H. (2011) · Science · doi:10.1126/science.1204265 · Cited by 2,089
Park, E. J., Lee, J. H., Yu, G.-Y., He, G., Ali, S. R., Holzer, R. G., Österreicher, C. H., Takahashi, H., & Karin, M. (2010) · Cell · doi:10.1016/j.cell.2009.12.052 · Cited by 1,764
Self-citationProtein Sensors for Membrane Sterols
Goldstein, J. L., DeBose-Boyd, R. A., & Brown, M. S. (2006) · Cell · doi:10.1016/j.cell.2005.12.022 · Cited by 1,517
Anderson, E. J., Lustig, M. E., Boyle, K. E., Woodlief, T. L., Kane, D. A., Lin, C.-T., Price, J. W., Kang, L., Rabinovitch, P. S., Szeto, H. H., et al. (2009) · Journal of Clinical Investigation · doi:10.1172/jci37048 · Cited by 1,253
Endoplasmic reticulum stress in liver disease
Malhi, H., & Kaufman, R. J. (2010) · Journal of Hepatology · doi:10.1016/j.jhep.2010.11.005 · Cited by 1,195
Self-citationMaeda, S., Kamata, H., Luo, J., Leffert, H. L., & Karin, M. (2005) · Cell · doi:10.1016/j.cell.2005.04.014 · Cited by 1,160
Self-citationRegulation of Hepatic Lipogenesis by the Transcription Factor XBP1
Lee, A., Scapa, E. F., Cohen, D. E., & Glimcher, L. H. (2008) · Science · doi:10.1126/science.1158042 · Cited by 1,000
Nonalcoholic Steatohepatitis: Definition and Pathology
Brunt, E. M. (2001) · Seminars in Liver Disease · doi:10.1055/s-2001-12925 · Cited by 915
Kammoun, H. L., Chabanon, H., Hainault, I., Luquet, S., Magnan, C., Koike, T., Ferré, P., & Foufelle, F. (2009) · Journal of Clinical Investigation · doi:10.1172/jci37007 · Cited by 732
Persistent activation of Nrf2 through p62 in hepatocellular carcinoma cells
Inami, Y., Waguri, S., Sakamoto, A., Kouno, T., Nakada, K., Hino, O., Watanabe, S., Ando, J., Iwadate, M., Yamamoto, M. P., et al. (2011) · The Journal of Cell Biology · doi:10.1083/jcb.201102031 · Cited by 615
Activation and Dysregulation of the Unfolded Protein Response in Nonalcoholic Fatty Liver Disease
Puri, P., Mirshahi, F., Cheung, O., Natarajan, R., Maher, J. W., Kellum, J. M., & Sanyal, A. J. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.10.039 · Cited by 615
Rutkowski, D. T., Wu, J., Back, S.-H., Callaghan, M. U., Ferris, S. P., Iqbal, J., Clark, R. L., Miao, H. Z., Hassler, J. R., Fornek, J. L., et al. (2008) · Developmental Cell · doi:10.1016/j.devcel.2008.10.015 · Cited by 580
Self-citationChen, C., Yang, H., Yang, W., Liu, C., Chen, P., You, S., Wang, L., Sun, C., Lu, S., Chen, D., et al. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.03.073 · Cited by 548
Sakurai, T., He, G., Matsuzawa, A., Yu, G.-Y., Maeda, S., Hardiman, G., & Karin, M. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.06.016 · Cited by 487
Self-citationHe, G., Dhar, D., Nakagawa, H., Font-Burgada, J., Ogata, H., Jiang, Y., Shalapour, S., Seki, E., Yost, S. E., Jepsen, K., et al. (2013) · Cell · doi:10.1016/j.cell.2013.09.031 · Cited by 476
Self-citationNASH is an Infl ammatory Disorder: Pathogenic, Prognostic and Therapeutic Implications
Farrell, G. C., Rooyen, D. M. V., Gan, L. T., & Chitturi, S. (2012) · Gut and Liver · doi:10.5009/gnl.2012.6.2.149 · Cited by 408
Ota, T., Gayet, C., & Ginsberg, H. N. (2008) · Journal of Clinical Investigation · doi:10.1172/jci32752 · Cited by 393
Complete hepatic regeneration after somatic deletion of an albumin-plasminogen activator transgene
Sandgren, E. P., Palmiter, R. D., Heckel, J. L., Daugherty, C. C., Brinster, R. L., & Degen, J. L. (1991) · Cell · doi:10.1016/0092-8674(91)90615-6 · Cited by 392
A Lymphotoxin-Driven Pathway to Hepatocellular Carcinoma
Haybaeck, J., Zeller, N., Wolf, M. J., Weber, A., Wagner, U., Kurrer, M. O., Bremer, J., Iezzi, G., Graf, R., Clavien, P., et al. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.08.021 · Cited by 381
Self-citationMaintenance of metabolic homeostasis by Sestrin2 and Sestrin3
Lee, J. H., Budanov, A. V., Talukdar, S., Park, E. J., Park, H. L., Park, H.-W., Bandyopadhyay, G., Li, N., Aghajan, M., Jang, I., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.08.004 · Cited by 295
Self-citationSaturated Fatty Acids Induce c-Src Clustering within Membrane Subdomains, Leading to JNK Activation
Holzer, R. G., Park, E., Li, N., Tran, H., Chen, M. F., Choi, C., Solinas, G., & Karin, M. (2011) · Cell · doi:10.1016/j.cell.2011.08.034 · Cited by 283
Self-citationSilencing of Lipid Metabolism Genes through IRE1α-Mediated mRNA Decay Lowers Plasma Lipids in Mice
So, J., Hur, K. Y., Tarrio, M. L., Ruda, V. M., Frank-Kamenetsky, M. D., Fitzgerald, K. J., Koteliansky, V., Lichtman, A. H., Iwawaki, T., Glimcher, L. H., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.09.004 · Cited by 280
Hepatocellular ballooning in NASH
Caldwell, S. H., Ikura, Y., Dias, D., Isomoto, K., Yabu, A., Moskaluk, C. A., Pramoonjago, P., Simmons, W., Scruggs, H., Rosenbaum, N., et al. (2010) · Journal of Hepatology · doi:10.1016/j.jhep.2010.04.031 · Cited by 250
Salomao, M. A., Remotti, H. E., VAUGHAN, R. D., Siegel, A. B., Lefkowitch, J. H., & Moreira, R. K. (2011) · Human Pathology · doi:10.1016/j.humpath.2011.07.005 · Cited by 178
Hepatocyte Transplantation into Diseased Mouse Liver
Weglarz, T. C., Degen, J. L., & Sandgren, E. P. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64835-3 · Cited by 149
Endoplasmic reticulum stress response in cancer: molecular mechanism and therapeutic potential.
Wang, G., Yang, Z. Q., & Zhang, K. (2010) · PubMed Central · Cited by 146
Calle, E. E., Teras, L. R., & Thun, M. J. (2005) · New England Journal of Medicine · doi:10.1056/nejm200511173532020 · Cited by 126
DeZwaan-McCabe, D., Riordan, J. D., Arensdorf, A. M., Icardi, M. S., Dupuy, A. J., & Rutkowski, D. T. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003937 · Cited by 90
Qiu, W., Zhang, J., Dekker, M. J., Wang, H., Huang, J., Brumell, J. H., & Adeli, K. (2011) · Hepatology · doi:10.1002/hep.24269 · Cited by 66
Stress Signaling in the Methionine-Choline–Deficient Model of Murine Fatty Liver Disease
Soon, R. K., Yan, J. S., Grenert, J. P., & Maher, J. J. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.07.046 · Cited by 57
Obesity, Inflammatory Signaling, and Hepatocellular Carcinoma—An Enlarging Link
Toffanin, S., Friedman, S. L., & Llovet, J. M. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.01.018 · Cited by 53
Adalimumab Could Suppress the Activity of Non Alcoholic Steatohepatitis (NASH)
Schramm, C., Schneider, A. R. J., Marx, A., & Lohse, A. (2008) · Zeitschrift für Gastroenterologie · doi:10.1055/s-2008-1027411 · Cited by 48
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Self-citationMechanisms of NAFLD development and therapeutic strategies
Friedman, S. L., Neuschwander-Tetri, B. A., Rinella, M., & Sanyal, A. J. (2018) · Nature Medicine · doi:10.1038/s41591-018-0104-9 · Cited by 4,354
NF-κB, inflammation, immunity and cancer: coming of age
Taniguchi, K., & Karin, M. (2018) · Nature Reviews Immunology · doi:10.1038/nri.2017.142 · Cited by 2,679
Self-citationInflammation in obesity, diabetes, and related disorders
Rohm, T. V., Meier, D. T., Olefsky, J. M., & Donath, M. Y. (2022) · Immunity · doi:10.1016/j.immuni.2021.12.013 · Cited by 2,066
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Metadata
- Authors
- Nakagawa, H., Umemura, A., Taniguchi, K., Font-Burgada, J., Dhar, D., Ogata, H., Zhong, Z., Valasek, M. A., Seki, E., Hidalgo, J., Koike, K., Kaufman, R. J., & Karin, M.
- Affiliations
- University of California San Diego (US)
- Kyushu University (JP)
- Universitat Autònoma de Barcelona (ES)
- The University of Tokyo (JP)
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Corresponding author
- Karin, Michael
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2014-09
- Volume
- 26
- Issue
- 3
- Pages
- 331-343
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC4165611
- OpenAlex
- W2085390667
- Cited by
- 525
- References
- 38
- Citations by year
- 2026: 22 · 2025: 38 · 2024: 43 · 2023: 58 · 2022: 57 · 2021: 57 · 2020: 56 · 2019: 40 · 2018: 42 · 2017: 34 · 2016: 39 · 2015: 28 · 2014: 11
- FWCI
- 18.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Japan Society for the Promotion of Science (24390183)
- National Heart, Lung, and Blood Institute (R01HL052173, HL052173-16)
- National Cancer Institute (R01CA118165, CA155120-02, R01CA155120, P30CA023100, CA118165-06)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK088227, DK042394-18, DK088227-06)
- National Institute of Environmental Health Sciences (P42ES010337)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Keywords
- endoplasmic reticulum stress, overnutrition, hepatocellular carcinoma, nonalcoholic steatohepatitis, TNF-α, plasminogen activator, high-fat diet, insulin resistance, hepatic steatosis, inflammatory macrophages, lipogenesis
- MeSH terms
- Endoplasmic Reticulum Chaperone BiP, Animals, Cells, Cultured, Fatty Liver, Heat-Shock Proteins, Carcinoma, Hepatocellular, Liver Neoplasms, Experimental, Male, Mice, Transgenic, Tumor Necrosis Factor-alpha, Urokinase-Type Plasminogen Activator, Signal Transduction, Overnutrition, Tumor Burden, Receptors, Tumor Necrosis Factor, Type I, Lipogenesis, Mice, Diet, High-Fat, Endoplasmic Reticulum Stress
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