Activating CAR and β-catenin induces uncontrolled liver growth and tumorigenesis
Open accessAbstract
Aberrant β-catenin activation contributes to a third or more of human hepatocellular carcinoma (HCC), but β-catenin activation alone is not sufficient to induce liver cancer in mice. Differentiated hepatocytes proliferate upon acute activation of either β-catenin or the nuclear xenobiotic receptor CAR. These responses are strictly limited and are tightly linked, since β-catenin is activated in nearly all of the CAR-dependent tumours generated by the tumour promoter phenobarbital. Here, we show that full activation of β-catenin in the liver induces senescence and growth arrest, which is overcome by combined CAR activation, resulting in uncontrolled hepatocyte proliferation, hepatomegaly and rapid lethality despite maintenance of normal liver function. Combining CAR activation with limited β-catenin activation induces tumorigenesis, and the tumours share a conserved gene expression signature with β-catenin-positive human HCC. These results reveal an unexpected route for hepatocyte proliferation and define a murine model of hepatocarcinogenesis with direct relevance to human HCC. Activation of the liver receptor CAR and β-catenin are both involved in hepatocellular carcinoma. Here, the authors show that combined activation of both CAR and β-catenin in mice can drive uncontrolled liver growth and is sufficient for hepatocarcinogenesis.
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
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?
Activating CTNNB1 mutations on their own may not be sufficient to drive cancer.
“Given that activating CTNNB1 mutations on their own may not be sufficient to drive cancer (26), we sought to co-mutate another gene that would accelerate cancer development.”
From The origin of hepatocellular carcinoma depends on metabolic zonation (2026) · cites this paper as [26]
The Introduction and Discussion state that β-catenin activation alone does not induce spontaneous liver tumors in mouse models, indicating that additional hits are needed. The Results likewise report that β-catenin activation alone did not induce liver tumors in the tested mice. This supports the cautious claim for mouse liver cancer, but the paper does not establish it for cancer generally. (LLM, conf=0.78)
Experimental — accuracy not yet measuredCombined pharmacologic activation of CAR and genetic activation of β-catenin in mice is sufficient to induce liver tumors sharing an extensive gene expression signature with a subset of human HCC displaying β-catenin activation.
“We have recently shown that combined pharmacologic activation of CAR and genetic activation of β-catenin in mice is sufficient to induce liver tumors that share an extensive gene expression signature with a subset of human HCC displaying β-catenin activation (Dong et al., 2015).”
From Circadian Homeostasis of Liver Metabolism Suppresses Hepatocarcinogenesis (2016) · cites this paper as Dong et al., 2015
The tumor-promoting function of CAR is tightly associated with β-catenin activation or mutation.
“The tumor promoting function of CAR is tightly associated with β-catenin activation or mutation (Dong et al., 2015; Loeppen et al., 2002).”
From Circadian Homeostasis of Liver Metabolism Suppresses Hepatocarcinogenesis (2016) · cites this paper as Dong et al., 2015
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Sorafenib in advanced hepatocellular carcinoma
Llovet, J. M., Ricci, S., Mazzaferro, V., Hilgard, P., Gane, E., Blanc, J.-F., de Oliveira, A. C., Santoro, A., Raoul, J.-L., Forner, A., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0708857 · Cited by 13,097 · see citing works
A New Era of Systemic Therapy for Hepatocellular Carcinoma with Regorafenib and Lenvatinib
Kudo, M. (2017) · Liver Cancer · doi:10.1159/000462153 · Cited by 5,974 · see citing works
Wnt/β-catenin signaling and disease
Clevers, H., & Nusse, R. (2012) · Cell · doi:10.1016/j.cell.2012.05.012 · Cited by 5,554 · see citing works
Identification of c- <i>MYC</i> as a Target of the APC Pathway
He, T.-C., Sparks, A. B., Rago, C., Hermeking, H., Zawel, L., da Costa, L. T., Morin, P. J., Vogelstein, B., & Kinzler, K. W. (1998) · Science · doi:10.1126/science.281.5382.1509 · Cited by 4,566 · see citing works
El-Serag, H. B. (2011) · New England Journal of Medicine · doi:10.1056/nejmra1001683 · Cited by 3,529 · see citing works
Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas
Xue, W., Zender, L., Miething, C., Dickins, R. A., Hernando, E., Krizhanovsky, V., Cordon-Cardo, C., & Lowe, S. W. (2007) · Nature · doi:10.1038/nature05529 · Cited by 2,473 · see citing works
The cyclin D1 gene is a target of the β-catenin/LEF-1 pathway
Shtutman, M., Zhurinsky, J., Simcha, I., Albanese, C., D’Amico, M., Pestell, R., & Ben-Ze’ev, A. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.10.5522 · Cited by 2,230 · see citing works
Somatic mutations of the β-catenin gene are frequent in mouse and human hepatocellular carcinomas
Coste, A. D. L., Romagnolo, B., Billuart, P., Renard, C.-A., Buendia, M., Soubrane, O., Fabrè, M., Chelly, J., Beldjord, C., Kahn, A., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.15.8847 · Cited by 1,121 · see citing works
Batlle, E., Henderson, J. T., Beghtel, H., van den Born, M., Sancho, E., Huls, G. A., Meeldijk, J., Robertson, J. V., van de Wetering, M., Pawson, T. J., et al. (2002) · Cell · doi:10.1016/s0092-8674(02)01015-2 · Cited by 1,118 · see citing works
Gene Expression Patterns in Human Liver Cancers
Chen, X., Cheung, S., So, S. K., Fan, S. T., Barry, C. T., Higgins, J., Lai, K.-M., Ji, J., Dudoit, S., Ng, I. O., et al. (2002) · Molecular Biology of the Cell · doi:10.1091/mbc.02-02-0023 · Cited by 879 · see citing works
GSK-3-Selective Inhibitors Derived from Tyrian Purple Indirubins
Meijer, L., Skaltsounis, A., Magiatis, P., Polychronopoulos, P., Knockaert, M., Leost, M., Ryan, X. P., Vonica, A., Brivanlou, A. H., Dajani, R., et al. (2003) · Chemistry & Biology · doi:10.1016/j.chembiol.2003.11.010 · Cited by 814 · see citing works
β-Catenin-Driven Cancers Require a YAP1 Transcriptional Complex for Survival and Tumorigenesis
Rosenbluh, J., Nijhawan, D., Cox, A. G., Li, X., Neal, J. T., Schafer, E. J., Zack, T. I., Wang, X., Tsherniak, A., Schinzel, A. C., et al. (2012) · Cell · doi:10.1016/j.cell.2012.11.026 · Cited by 757 · see citing works
Augmented Wnt signaling in a mammalian model of accelerated aging
Liu, H., Fergusson, M. M., Castilho, R. M., Liu, J., Cao, L., Chen, J., Malide, D., Rovira, I. I., Schimel, D., Kuo, C. J., et al. (2007) · Science · doi:10.1126/science.1143578 · Cited by 755 · cited 2× · see citing works
“We found that chronic activation of Wnt/ β -catenin alone induces senescence in the liver, as previously observed in the gut 26 and skin 12 , and demonstrated that CAR activation overcomes this block to β -catenin induced growth.”
Epidemiology of hepatocellular carcinoma in the United States: Where are we? Where do we go?
El‐Serag, H. B., & Kanwal, F. (2014) · Hepatology · doi:10.1002/hep.27222 · Cited by 645 · see citing works
Wang, I.-C., Chen, Y.-J., Hughes, D., Petrovic, V., Major, M. L., Park, H. J., Tan, Y., Ackerson, T., & Costa, R. H. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.24.10875-10894.2005 · Cited by 627 · see citing works
Anders, L., Ke, N., Hydbring, P., Choi, Y. J., Widlund, H. R., Chick, J. M., Zhai, H., Vidal, M., Gygi, S. P., Braun, P., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.10.001 · Cited by 543 · see citing works
Role of the SCFSkp2 Ubiquitin Ligase in the Degradation of p21Cip1 in S Phase
Bornstein, G., Bloom, J., Sitry-Shevah, D., Nakayama, K., Pagano, M., & Hershko, A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301774200 · Cited by 496 · see citing works
Dysregulation of Wnt/β-Catenin Signaling in Gastrointestinal Cancers
White, B. D., Chien, A. J., & Dawson, D. W. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.12.001 · Cited by 471 · see citing works
Cancer genetics and genomics of human FOX family genes
Katoh, M., Igarashi, M., Fukuda, H., Nakagama, H., & Katoh, M. (2012) · Cancer Letters · doi:10.1016/j.canlet.2012.09.017 · Cited by 401 · see citing works
Skp2-Mediated Degradation of p27 Regulates Progression into Mitosis
Nakayama, K., Nagahama, H., Minamishima, Y. A., Miyake, S., Ishida, N., Hatakeyama, S., Kitagawa, M., Iemura, S.-I., Natsume, T., & Nakayama, K. (2004) · Developmental Cell · doi:10.1016/s1534-5807(04)00131-5 · Cited by 364 · see citing works
Kalinichenko, V. V., Major, M. L., Wang, X., Petrovic, V., Kuechle, J., Yoder, H. M., Dennewitz, M. B., Shin, B., Datta, A., Raychaudhuri, P., et al. (2004) · Genes & Development · doi:10.1101/gad.1200704 · Cited by 358 · see citing works
Yamamoto, Y., Moore, R., Goldsworthy, T. L., Negishi, M., & Maronpot, R. R. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-1459 · Cited by 350 · see citing works
Linking β-Catenin to Androgen-signaling Pathway
Yang, F., Li, X., Sharma, M., Sasaki, C. Y., Longo, D. L., Lim, B., & Sun, Z. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111962200 · Cited by 342 · see citing works
Self-citationGenetics of hepatocellular tumors
Laurent‐Puig, P., & Zucman‐Rossi, J. (2006) · Oncogene · doi:10.1038/sj.onc.1209547 · Cited by 317 · see citing works
Huang, W., Zhang, J., Washington, M., Liu, J., Parant, J. M., Lozano, G., & Moore, D. D. (2005) · Molecular Endocrinology · doi:10.1210/me.2004-0520 · Cited by 284 · see citing works
Self-citationDamalas, A., Kahan, S., Shtutman, M. S., Ben‐Ze'ev, A., & Oren, M. (2001) · The EMBO Journal · doi:10.1093/emboj/20.17.4912 · Cited by 206 · see citing works
Zhang, D., Wang, H., & Tan, Y. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021397 · Cited by 199 · see citing works
CKIα ablation highlights a critical role for p53 in invasiveness control
Elyada, E., Pribluda, A., Goldstein, R. E., Morgenstern, Y., Brachya, G., Cojocaru, G., Snir-Alkalay, I., Burstain, I., Haffner‐Krausz, R., Jung, S., et al. (2011) · Nature · doi:10.1038/nature09673 · Cited by 199 · see citing works
Hepatocarcinogenesis in Mice with β-Catenin and Ha-Ras Gene Mutations
Harada, N., Oshima, H., Katoh, M., Tamai, Y., Oshima, M., & Taketo, M. M. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-2123 · Cited by 194 · see citing works
T-cell factor 4 and β-catenin chromatin occupancies pattern zonal liver metabolism in mice
Gougelet, A., Torre, C., Veber, P., Sartor, C., Bachelot, L., Denechaud, P.-D., Godard, C., Moldes, M., Burnol, A.-F., Dubuquoy, C., et al. (2014) · Hepatology · doi:10.1002/hep.26924 · Cited by 190 · see citing works
Hepatomegaly in transgenic mice expressing an oncogenic form of beta-catenin.
Cadoret, A., Ovejero, C., Saadi-Kheddouci, S., Souil, E., Fabrè, M., Romagnolo, B., Kahn, A., & Perret, C. (2001) · PubMed · Cited by 169 · see citing works
Anson, M., Crain‐Denoyelle, A., Baud, V., Chereau, F., Gougelet, A., Terris, B., Yamagoe, S., Colnot, S., Viguier, M., Perret, C., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci43937 · Cited by 168 · see citing works
Role of Wnt/Beta-Catenin Signaling in Liver Metabolism and Cancer
Monga, S. (2009) · International Journal of Biochemistry and Cell Biology · doi:10.1016/j.biocel.2009.09.001 · Cited by 167 · see citing works
Aydinlik, H., Nguyen, T. D., Moennikes, O., Buchmann, A., & Schwarz, M. (2001) · Oncogene · doi:10.1038/sj.onc.1204982 · Cited by 164 · see citing works
Harada, N., Miyoshi, H., Murai, N., Oshima, H., Tamai, Y., Oshima, M., & Taketo, M. M. (2002) · PubMed · Cited by 164 · see citing works
Nejak-Bowen, K., Thompson, M. D., Singh, S., Bowen, W., Dar, M. J., Khillan, J., Dai, C.-S., & Monga, S. P. S. (2010) · Hepatology · doi:10.1002/hep.23538 · Cited by 160 · see citing works
Renard, C.-A., Labalette, C., Armengol, C., Cougot, D., Wei, Y., Cairo, S., Pineau, P., Neuveut, C., de Reyniès, A., Dejean, A., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-2344 · Cited by 157 · cited 1× · see citing works
“The upregulated genes also include at least 10 known or candidate β -catenin targets, such as the ephrin receptor EFB2 43 and the T-Box transcriptional repressor TBX3 44 , and also the Wnt pathway components LEF1 and TCF7.”
Millour, J., Constantinidou, D., Stavropoulou, A. V., Wilson, M., Myatt, S. S., Kwok, J. M.-M., Sivanandan, K., Coombes, R. C., Medema, R. H., Hartman, J., et al. (2010) · Oncogene · doi:10.1038/onc.2010.47 · Cited by 155 · see citing works
A cell-penetrating ARF peptide inhibitor of FoxM1 in mouse hepatocellular carcinoma treatment
Gusarova, G. A., Wang, I., Major, M. L., Kalinichenko, V. V., Ackerson, T. J., Petrovic, V., & Costa, R. H. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27527 · Cited by 154 · see citing works
Blanco‐Bose, W. E., Murphy, M. J., Ehninger, A., Offner, S., Dubey, C., Huang, W., Moore, D. D., & Trumpp, A. (2008) · Hepatology · doi:10.1002/hep.22475 · Cited by 138 · see citing works
Self-citationSixty-five gene-based risk score classifier predicts overall survival in hepatocellular carcinoma
Kim, S. M., Leem, S.-H., Chu, I., Park, Y.-Y., Kim, S. C., Kim, S. B., Park, E. S., Lim, J. Y., Heo, J., Kim, Y. J., et al. (2011) · Hepatology · doi:10.1002/hep.24813 · Cited by 132 · see citing works
Self-citation(2002) · PubMed · Cited by 120 · see citing works
Basu, S., Ellinger, B., Rizzo, S., Deraeve, C., Schürmann, M., Preut, H., Arndt, H., & Waldmann, H. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1015269108 · Cited by 103 · see citing works
Calvisi, D. F., Factor, V. M., Ladu, S., Conner, E. A., & Thorgeirsson, S. S. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.02.014 · Cited by 100 · see citing works
FoxM1c Counteracts Oxidative Stress-induced Senescence and Stimulates Bmi-1 Expression
Li, S. K. M., Smith, D. K., Leung, W. Y., Cheung, A. M. S., Lam, E. W. ‐., Dimri, G. P., & Yao, K. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m709604200 · Cited by 97 · see citing works
Gadd45β Is Induced Through a CAR-Dependent, TNF-Independent Pathway in Murine Liver Hyperplasia * #
Columbano, A., Ledda‐Columbano, G. M., Pibiri, M., Cossu, C., Menegazzi, M., Moore, D. D., Huang, W., Tian, J., & Locker, J. D. (2005) · Hepatology · doi:10.1002/hep.20883 · Cited by 91 · see citing works
Self-citationBraeuning, A., Sanna, R., Huelsken, J., & Schwarz, M. (2009) · Drug Metabolism and Disposition · doi:10.1124/dmd.108.026179 · Cited by 82 · see citing works
Qu, K., Xu, X., Liu, C., Wu, Q., Wei, J., Meng, F., Zhou, L., Wang, Z., Lei, L., & Liu, P. (2012) · Cancer Letters · doi:10.1016/j.canlet.2012.12.008 · Cited by 72 · see citing works
A review of epidemiological data on epilepsy, phenobarbital, and risk of liver cancer
Vecchia, C. L., & Negri, E. (2013) · European Journal of Cancer Prevention · doi:10.1097/cej.0b013e32836014c8 · Cited by 66 · see citing works
Rignall, B., Braeuning, A., Buchmann, A., & Schwarz, M. (2010) · Carcinogenesis · doi:10.1093/carcin/bgq226 · Cited by 63 · see citing works
Structural basis of coactivation of liver receptor homolog-1 by β-catenin
Yumoto, F., Nguyen, P., Sablin, E. P., Baxter, J. D., Webb, P., & Fletterick, R. J. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1117036108 · Cited by 63 · see citing works
Wu, Q., Liu, C., Tai, M., Liu, D., Lei, L., Wang, R., Tian, M., & Lü, Y. (2010) · Acta Pharmacologica Sinica · doi:10.1038/aps.2010.4 · Cited by 60 · see citing works
Cancer incidence among patients using antiepileptic drugs: a long-term follow-up of 28,000 patients
Lamminpää, A., Pukkala, ., Teppo, L., & Neuvonen, P. J. (2002) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-002-0429-6 · Cited by 60 · see citing works
Calvisi, D. F., Ladu, S., Factor, V. M., & Thorgeirsson, S. S. (2004) · Carcinogenesis · doi:10.1093/carcin/bgh083 · Cited by 55 · see citing works
Braeuning, A., Heubach, Y., Knorpp, T., Kowalik, M. A., Templin, M., Columbano, A., & Schwarz, M. (2011) · Toxicological Sciences · doi:10.1093/toxsci/kfr166 · Cited by 40 · see citing works
Promoting effects of 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene in mouse hepatocarcinogenesis
Dragani, T. A., Manenti, G., Galliani, G., & Porta, G. D. (1985) · Carcinogenesis · doi:10.1093/carcin/6.2.225 · Cited by 38 · see citing works
Hepatocellular carcinoma development induced by conditional β‐catenin activation in Lkb1+/− mice
Miyoshi, H., Deguchi, A., Nakau, M., Kojima, Y., Mori, A. S., Oshima, M., Aoki, M., & Taketo, M. M. (2009) · Cancer Science · doi:10.1111/j.1349-7006.2009.01284.x · Cited by 37 · see citing works
Ganzenberg, K., Singh, Y., & Braeuning, A. (2013) · Toxicology · doi:10.1016/j.tox.2013.03.019 · Cited by 29 · see citing works
Schreiber, S., Rignall, B., Braeuning, A., Marx‐Stoelting, P., Ott, T., Buchmann, A., Hammad, S., Hengstler, J. G., Schwarz, M., & Köhle, C. (2011) · Journal of Molecular Histology · doi:10.1007/s10735-011-9342-6 · Cited by 24 · see citing works
Wei, B., Edwards, J. B., Hoover, S. B., Tillman, H. S., Reed, L. T., Sills, R. C., & Simpson, R. M. (2008) · Toxicologic Pathology · doi:10.1177/0192623308327120 · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Circadian Homeostasis of Liver Metabolism Suppresses Hepatocarcinogenesis
Kettner, N. M., Voicu, H., Finegold, M. J., Coarfa, C., Sreekumar, A., Putluri, N., Katchy, C. A., Lee, C., Moore, D. D., & Fu, L. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.10.007 · Cited by 508 · see citing works
“We have recently shown that combined pharmacologic activation of CAR and genetic activation of βcatenin in mice is sufficient to induce liver tumors that share an extensive gene expression signature with a subset of human HCC displaying β-catenin activation (Dong et al., 2015).”
BackgroundSelf-citationMutations and mechanisms of WNT pathway tumour suppressors in cancer
Bugter, J. M., Fenderico, N., & Maurice, M. M. (2021) · Nature Reviews Cancer · doi:10.1038/s41568-020-00307-z · Cited by 466 · see citing works
The Hippo pathway in intestinal regeneration and disease
Hong, A. W., Meng, Z., & Guan, K. (2016) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2016.59 · Cited by 326 · see citing works
Nuclear receptors and nonalcoholic fatty liver disease
Cave, M. C., Clair, H. B., Hardesty, J., Falkner, K. C., Feng, W., Clark, B. J., Sidey, J., Shi, H., Aqel, B. A., McClain, C. J., et al. (2016) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2016.03.002 · Cited by 280 · see citing works
Exon 3 mutations of CTNNB1 drive tumorigenesis: a review
Gao, C., Wang, Y., Broaddus, R. R., Sun, L., Xue, F., & Zhang, W. (2017) · Oncotarget · doi:10.18632/oncotarget.23695 · Cited by 223 · see citing works
Molecular Pathogenesis of NASH
Caligiuri, A., Gentilini, A., & Marra, F. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17091575 · Cited by 212 · see citing works
Dong, B., Zhou, Y., Wang, W., Scott, J., Kim, K., Sun, Z., Guo, Q., Yang, L., Gonzales, N. M., Wu, H., et al. (2019) · Hepatology · doi:10.1002/hep.30937 · Cited by 185 · see citing works
Self-citationIL‐6 trans‐signaling is essential for the development of hepatocellular carcinoma in mice
Bergmann, J., Müller, M., Baumann, N., Reichert, M., Heneweer, C., Bolik, J., Lücke, K., Gruber, S., Carambia, A., Boretius, S., et al. (2017) · Hepatology · doi:10.1002/hep.28874 · Cited by 152 · see citing works
Molina-Sánchez, P., Ruiz de Galarreta, M., Yao, M. A., Lindblad, K. E., Bresnahan, E., Bitterman, E., Martin, T. C., Rubenstein, T., Nie, K., Golas, J., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.08.015 · Cited by 117 · see citing works
The Roles of Xenobiotic Receptors: Beyond Chemical Disposition
Mackowiak, B., Hodge, J., Stern, S., & Wang, H. (2018) · Drug Metabolism and Disposition · doi:10.1124/dmd.118.081042 · Cited by 116 · see citing works
Nuclear receptors as therapeutic targets in liver disease: are we there yet?
Rudraiah, S., Zhang, X., & Wang, L. (2016) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010715-103209 · Cited by 87 · see citing works
Felter, S. P., Foreman, J. E., Boobis, A., Corton, J. C., Doi, A. M., Flowers, L., Goodman, J., Haber, L. T., Jacobs, A., Klaunig, J. E., et al. (2018) · Regulatory Toxicology and Pharmacology · doi:10.1016/j.yrtph.2017.11.003 · Cited by 80 · see citing works
Regulation of gene expression by CAR: an update
Kobayashi, K., Hashimoto, M., Honkakoski, P., & Negishi, M. (2015) · Archives of Toxicology · doi:10.1007/s00204-015-1522-9 · Cited by 80 · see citing works
Lake, B. G. (2018) · Toxicology Research · doi:10.1039/c8tx00008e · Cited by 66 · see citing works
Clinical significance of APOB inactivation in hepatocellular carcinoma
Lee, G., Jeong, Y. S., Kim, D. W., Kwak, M. J., Koh, J., Joo, E. W., Lee, J., Kah, S., Sim, Y.-E., & Yim, S. Y. (2018) · Experimental & Molecular Medicine · doi:10.1038/s12276-018-0174-2 · Cited by 51 · see citing works
Self-citationBhushan, B., Stoops, J. W., Mars, W. M., Orr, A., Bowen, W. C., Paranjpe, S., & Michalopoulos, G. K. (2019) · Hepatology · doi:10.1002/hep.30109 · Cited by 49 · see citing works
Ejaeidi, A. A., Craft, B. S., Puneky, L. V., Lewis, R. E., & Cruse, J. M. (2015) · Experimental and Molecular Pathology · doi:10.1016/j.yexmp.2015.06.002 · Cited by 49 · see citing works
Carcinogenic activity of pentabrominated diphenyl ether mixture (DE-71) in rats and mice
Dunnick, J. K., Pandiri, A. R., Merrick, B. A., Kissling, G. E., CUNNY, H. C., Mutlu, E., Waidyanatha, S., Sills, R. C., Hong, H. L. T., Ton, T.-V. T., et al. (2018) · Toxicology Reports · doi:10.1016/j.toxrep.2018.05.010 · Cited by 48 · see citing works
Zhou, L., Zhang, W., Xie, W., Chen, H., Yu, W., Li, H., & Shen, G. (2017) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2017.06.071 · Cited by 43 · see citing works
Wnt Signaling in Adult Epithelial Stem Cells and Cancer
Tan, S. H., & Barker, N. (2018) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2017.11.017 · Cited by 41 · see citing works
Yamada, T., Cohen, S. M., & Lake, B. G. (2021) · Critical Reviews in Toxicology · doi:10.1080/10408444.2021.1939654 · Cited by 41 · see citing works
Lodato, N. J., Melia, T., Rampersaud, A., & Waxman, D. J. (2017) · Toxicological Sciences · doi:10.1093/toxsci/kfx114 · Cited by 38 · see citing works
Zahid, K. R., Yao, S., Khan, A. R. R., Raza, U., & Gou, D. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.01000 · Cited by 36 · see citing works
de Haan, L. R., van der Lely, S. J., Warps, A. K., Hofsink, Q., Olthof, P. B., de Keijzer, M. J., Lionarons, D. A., Dias, L. M., Bruinsma, B. G., Uygun, K., et al. (2018) · Journal of Clinical and Translational Research · doi:10.18053/jctres.04.201801.001 · Cited by 33 · see citing works
Lee, S. H., Yim, S. Y., Jeong, Y. S., Li, Q., Kang, S., Sohn, B. H., Kumar, S. V., Shin, J., Choi, Y. R., Shim, J., et al. (2022) · Hepatology · doi:10.1002/hep.32490 · Cited by 32 · see citing works
Self-citationLiu, Z., Hu, Y., Liang, H., Sun, Z., Feng, S., & Deng, H. (2016) · Journal of Proteome Research · doi:10.1021/acs.jproteome.5b01125 · Cited by 32 · see citing works
Schisandrol B promotes liver enlargement via activation of PXR and YAP pathways in mice
Zhao, Y.-Y., Yao, X., Jiao, T., Tian, J., Gao, Y., Fan, S., Chen, P., Jiang, Y., Zhou, Y., Chen, Y., et al. (2021) · Phytomedicine · doi:10.1016/j.phymed.2021.153520 · Cited by 31 · see citing works
MIF is a critical regulator of mononuclear phagocytic infiltration in hepatocellular carcinoma
Liao, Y., Wu, C., Yang, L., Wen, J., & Zhao, D. (2023) · iScience · doi:10.1016/j.isci.2023.107273 · Cited by 30 · see citing works
Wang, X., Zhou, Y., Wang, C., Zhao, Y., Cheng, Y., Yu, S., Li, X., Zhang, W., Zhang, Y., & Quan, H. (2022) · Clinical & Translational Oncology · doi:10.1007/s12094-022-02859-y · Cited by 29 · see citing works
Nuclear receptor CAR-mediated liver cancer and its species differences
Shizu, R., & Yoshinari, K. (2020) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2020.1746268 · Cited by 29 · see citing works
Clinical Relevance of the Constitutive Androstane Receptor
Stern, S., Kurian, R., & Wang, H. (2022) · Drug Metabolism and Disposition · doi:10.1124/dmd.121.000483 · Cited by 29 · see citing works
Xenosensor CAR mediates down-regulation of miR-122 and up-regulation of miR-122 targets in the liver
Kazantseva, Y. A., Yarushkin, A. A., Mostovich, L. A., Pustylnyak, Y. A., & Pustylnyak, V. O. (2015) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2015.07.004 · Cited by 27 · see citing works
Tong, H., Liu, X., Li, T., Qiu, W., Peng, C., Shen, B., & Zhu, Z. (2020) · OncoTargets and Therapy · doi:10.2147/ott.s237804 · Cited by 26 · see citing works
Shizu, R., Min, J., Sobhany, M., Pedersen, L. C., Mutoh, S., & Negishi, M. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.806604 · Cited by 25 · see citing works
The origin of hepatocellular carcinoma depends on metabolic zonation
Guo, J., Liang, R., Chung, A., Li, Z., Li, B., Chen, E., Li, L., Wang, J., Hsieh, M.-H., Fang, I. X., et al. (2026) · Science · doi:10.1126/science.adv7129 · Cited by 24 · see citing works
Tumor promotion and inhibition by phenobarbital in livers of conditional Apc-deficient mice
Braeuning, A., Gavrilov, A., Geissler, M., Wenz, C., Colnot, S., Templin, M. F., Metzger, U., Römer, M., Zell, A., & Schwarz, M. (2016) · Archives of Toxicology · doi:10.1007/s00204-016-1667-1 · Cited by 23 · see citing works
Exploring the Impact of the β-Catenin Mutations in Hepatocellular Carcinoma: An In-Depth Review
Idrissi, Y. A., Rajabi, M. R., Beumer, J. H., Monga, S. P., & Saeed, A. (2024) · Cancer Control · doi:10.1177/10732748241293680 · Cited by 23 · see citing works
Role of the constitutive androstane receptor (CAR) in human liver cancer
Bae, S. D. W., Nguyen, R., Qiao, L., & George, J. (2021) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2021.188516 · Cited by 22 · see citing works
Bhushan, B., Molina, L., Koral, K., Stoops, J. W., Mars, W. M., Banerjee, S., Orr, A., Paranjpe, S., Monga, S. P., Locker, J., et al. (2021) · Hepatology · doi:10.1002/hep.31521 · Cited by 20 · see citing works
Yim, S. Y., Shim, J., Shin, J., Jeong, Y. S., Kang, S., Kim, S.-B., Eun, Y., Lee, D. J., Conner, E. A., Factor, V. M., et al. (2018) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-18-0313 · Cited by 20 · see citing works
Self-citationShizu, R., Makida, N., Sobe, K., Ishimura, M., Takeshita, A., Hosaka, T., Kanno, Y., Sasaki, T., & Yoshinari, K. (2023) · Toxicological Sciences · doi:10.1093/toxsci/kfad129 · Cited by 19 · see citing works
Diindoles produced from commensal microbiota metabolites function as endogenous CAR/Nr1i3 ligands
Liu, J., Malekoltojari, A., Asokakumar, A., Chow, V., Li, L., Li, H., Grimaldi, M., Dang, N., Campbell, J., Barrett, H., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-46559-3 · Cited by 19 · see citing works
Impact of CAR Agonist Ligand TCPOBOP on Mouse Liver Chromatin Accessibility
Lodato, N. J., Rampersaud, A., & Waxman, D. J. (2018) · Toxicological Sciences · doi:10.1093/toxsci/kfy070 · Cited by 18 · see citing works
Kazantseva, Y. A., Pustylnyak, Y. A., & Pustylnyak, V. O. (2016) · Biochemistry (Moscow) · doi:10.1134/s0006297916040040 · Cited by 17 · see citing works
Hori, T., Saito, K., Moore, R., Flake, G. P., & Negishi, M. (2018) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-18-0118 · Cited by 17 · see citing works
Mattu, S., Saliba, C., Sulas, P., Zavattari, P., Perra, A., Kowalik, M. A., Monga, S. P., & Columbano, A. (2018) · American Journal Of Pathology · doi:10.1016/j.ajpath.2018.07.022 · Cited by 16 · see citing works
Data mining of the expression and regulatory role of BCAT1 in hepatocellular carcinoma
Zou, H., Liao, M., Xu, W., Yao, R., & Liao, W. (2019) · Oncology Letters · doi:10.3892/ol.2019.10932 · Cited by 16 · see citing works
Yamada, T., Ôhara, A., Ozawa, N., Maeda, K., Kondo, M., Okuda, Y., Abe, J., Cohen, S. M., & Lake, B. G. (2020) · Toxicological Sciences · doi:10.1093/toxsci/kfaa125 · Cited by 16 · see citing works
Ôhara, A., Takahashi, Y., Kondo, M., Okuda, Y., Takeda, S., Kushida, M., Kobayashi, K., Sumida, K., & Yamada, T. (2017) · Toxicology Research · doi:10.1039/c7tx00163k · Cited by 16 · see citing works
Does school breakfast benefit children's educational performance?
Fernald, L. C. H., Ani, C. C., & Grantham‐McGregor, S. (1997) · PubMed · Cited by 16 · see citing works
Niehoff, N. M., Zabor, E. C., Satagopan, J. M., Widell, A., OʼBrien, T. R., Zhang, M., Rothman, N., Grimsrud, T. K., Eeden, S. K. V. D., & Engel, L. S. (2020) · Environmental Research · doi:10.1016/j.envres.2020.109690 · Cited by 15 · see citing works
Rampersaud, A., Lodato, N. J., Shin, A., & Waxman, D. J. (2019) · Toxicological Sciences · doi:10.1093/toxsci/kfz148 · Cited by 15 · see citing works
Yamada, T., Cohen, S. M., & Lake, B. G. (2025) · Critical Reviews in Toxicology · doi:10.1080/10408444.2025.2513332 · Cited by 14 · see citing works
Park, H., Park, H., Baek, J., Moon, H., & Ro, S. W. (2022) · Biology · doi:10.3390/biology11040585 · Cited by 14 · see citing works
β-catenin signaling, the constitutive androstane receptor and their mutual interactions
Braeuning, A., & Pávek, P. (2020) · Archives of Toxicology · doi:10.1007/s00204-020-02935-8 · Cited by 13 · see citing works
Collino, A., Termanini, A., Nicoli, P., Diaferia, G., Polletti, S., Recordati, C., Castiglioni, V., Caruso, D., Mitro, N., Natoli, G., et al. (2018) · PLOS Genetics · doi:10.1371/journal.pgen.1007380 · Cited by 13 · see citing works
D’Ambrosio, A., Bressan, D., Ferracci, E., Carbone, F. G., Mulé, P., Rossi, F., Barbieri, C., Sorrenti, E., Fiaccadori, G., Detone, T., et al. (2024) · Science Advances · doi:10.1126/sciadv.adh4435 · Cited by 12 · see citing works
Yamada, T. (2021) · Journal of Toxicologic Pathology · doi:10.1293/tox.2021-0027 · Cited by 12 · see citing works
Microbiota-mediated reactivation of triclosan oxidative metabolites in colon tissues
Zhang, H., Sanidad, K. Z., Zhang, J., Wang, G., Zhang, R., Hu, C., Lin, Y., Haggerty, T. D., Parsonnet, J., Zheng, Y., et al. (2022) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2022.130509 · Cited by 11 · see citing works
Küblbeck, J., Zancanella, V., Prantner, V., Molnár, F., Squires, E. J., Dacasto, M., Honkakoski, P., & Giantin, M. (2015) · Xenobiotica · doi:10.3109/00498254.2015.1060374 · Cited by 11 · see citing works
Constitutive androstane receptor activation evokes the expression of glycolytic genes
Yarushkin, A. A., Kazantseva, Y. A., Prokopyeva, E. A., Markova, D. N., Pustylnyak, Y. A., & Pustylnyak, V. O. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.08.075 · Cited by 9 · see citing works
DNA Methylation Changes in Tbx3 in a Mouse Model Exposed to Polybrominated Diphenyl Ethers
Shimbo, T., Dunnick, J. K., Brix, A. E., Mav, D., Shah, R., Roberts, J. D., & Wade, P. A. (2017) · International Journal of Toxicology · doi:10.1177/1091581817706676 · Cited by 9 · see citing works
Fujino, C., Sanoh, S., Tateno, C., Ohta, S., & Kotake, Y. (2019) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2019.03.010 · Cited by 9 · see citing works
Sidaway, J. E., Orton, T. C., Kalaitzi, K., Jones, H. B., Foster, A. J., & Lake, B. G. (2019) · Toxicology · doi:10.1016/j.tox.2019.152343 · Cited by 8 · see citing works
Progression of Hepatic Adenoma to Carcinoma in Ogg1 Mutant Mice Induced by Phenobarbital
Kakehashi, A., Ishii, N., Okuno, T., Fujioka, M., Gi, M., Fukushima, S., & Wanibuchi, H. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/8541064 · Cited by 8 · see citing works
Ahmed, K. A., Alqaisi, K. M., Ibrahim, N. A., Abdullah, S. S., Jabbar, A. A., Saleh, G. N., Alsharayiah, D. K., Algefare, A. I., Zainel, M. A., Alfwuaires, M. A., et al. (2025) · BMC Pharmacology and Toxicology · doi:10.1186/s40360-025-01041-8 · Cited by 7 · see citing works
Rohr, M., Aljabban, J., Rudeski-Rohr, T., Lessans, S., Nakkina, S. P., Hadley, D., Zhu, X., & Altomare, D. A. (2021) · Clinical and Translational Gastroenterology · doi:10.14309/ctg.0000000000000295 · Cited by 7 · see citing works
Noncanonical Constitutive Androstane Receptor Signaling in Gene Regulation
Pustylnyak, Y. A., Gulyaeva, L. F., & Pustylnyak, V. O. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186735 · Cited by 6 · see citing works
Riegler, T., Nejabat, M., Eichner, J., Stiebellehner, M., Subosits, S., Bilban, M., Zell, A., Huber, W. W., Schulte‐Hermann, R., & Grasl‐Kraupp, B. (2015) · Carcinogenesis · doi:10.1093/carcin/bgv135 · Cited by 6 · see citing works
Dusek, J., Škoda, J., Holas, O., Štefela, A., Smutný, T., Linhartová, L., Hirsova, P., Kučera, O., Mičuda, S., Braeuning, A., et al. (2019) · Toxicology Letters · doi:10.1016/j.toxlet.2019.05.024 · Cited by 6 · see citing works
Xenobiotic Receptor CAR Is Highly Induced in Psoriasis and Promotes Keratinocyte Proliferation
Lai, B., Xie, X., Li, F., Cui, Q., Dang, E., Luo, W., Wang, N., Zheng, Y., Wang, G., Xiao, L., et al. (2021) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2021.05.017 · Cited by 5 · see citing works
Hepatic Nuclear Receptors in Cholestasis-to-Cholangiocarcinoma Pathology
Cheon, I., Kim, M., Kim, K. H., & Ko, S. (2024) · American Journal Of Pathology · doi:10.1016/j.ajpath.2024.07.023 · Cited by 5 · see citing works
Endonucleosis mediates internalization of cytoplasm into the nucleus
Galanopoulou, O., Tachmatzidi, E. C., Deligianni, E., Botskaris, D., Nikolaou, K. C., Gargani, S., Dalezios, Y., Chalepakis, G., & Talianidis, I. (2024) · Nature Communications · doi:10.1038/s41467-024-50259-3 · Cited by 4 · see citing works
Cytochrome P450 enzymes as modulators of oncogenic signaling via the Wnt/β-catenin signaling pathway
Braeuning, A. (2026) · Archives of Toxicology · doi:10.1007/s00204-025-04295-7 · Cited by 3 · see citing works
Koral, K., Bhushan, B., Orr, A. V., Stoops, J. W., Bowen, W. C., Copeland, M. A., Locker, J. D., Mars, W. M., & Michalopoulos, G. K. (2022) · American Journal Of Pathology · doi:10.1016/j.ajpath.2022.03.010 · Cited by 3 · see citing works
Kerger, B. D., Bogen, K. T., Loccisano, A. E., & Lamb, J. C. (2017) · Human and Ecological Risk Assessment An International Journal · doi:10.1080/10807039.2017.1408397 · Cited by 3 · see citing works
CAR takes care of the injured liver
Bachofner, M., & Werner, S. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.03.018 · Cited by 3 · see citing works
Nanoparticle-mediated delivery of peptide-based degraders enables targeted protein degradationPreprint
Ghosal, S., Robertus, C. M., Wang, J., Chan, H. W., Alamgir, A., Almonte, J., & Alabi, C. A. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.03.17.584721 · Cited by 3 · see citing works
Biphasic hCAR Inhibition-Activation by Two Aminoazo Liver Carcinogens
Bogen, K. T. (2018) · Nuclear Receptor Research · doi:10.11131/2018/101321 · Cited by 2 · see citing works
Kuwata, K., Inoue, K., Ichimura, R., Takahashi, M., Kodama, Y., Shibutani, M., & Yoshida, M. (2017) · Toxicologic Pathology · doi:10.1177/0192623317708898 · Cited by 2 · see citing works
de Oliveira, S., Houseright, R. A., Graves, A. L., Golenberg, N., Korte, B. G., Miskolci, V., & Huttenlocher, A. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/299016 · Cited by 2 · see citing works
Zhang, Z., Ding, F., & Zhang, Z. (2025) · Apmis · doi:10.1111/apm.70060 · Cited by 1 · see citing works
Yu, K., Chen, M., Hou, W., Lu, J., Liu, Q., Zeng, W., Du, Z., Hou, X., Hao, E., & Deng, J. (2026) · Human Mutation · doi:10.1155/humu/1465989 · Cited by 1 · see citing works
Circadian clock‐mediated nuclear receptors in cancer
Niu, Y., & Tang, S. (2022) · Journal of Cellular Physiology · doi:10.1002/jcp.30905 · Cited by 1 · see citing works
Gao, Y., Cai, C., Zheng, W., Fan, S., Zhang, Y., Zhou, Y., Li, H., Yang, J., Guan, S., & Bi, H. (2025) · Drug Metabolism and Disposition · doi:10.1016/j.dmd.2025.100092 · Cited by 1 · see citing works
Functional Characterization of a Novel Variant of the Constitutive Androstane Receptor (CAR, NR1I3)
Prantner, V., Cinnamon, Y., Küblbeck, J., Molnár, F., & Honkakoski, P. (2018) · Nuclear Receptor Research · doi:10.32527/2018/101386 · Cited by 1 · see citing works
Constitutive Androstane Receptor
Yan, J., & Xie, W. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.95606-x · Cited by 1 · see citing works
Nanoparticle-mediated delivery of peptide-based degraders enables targeted protein degradationPreprint
Alabi, C. A., Ghosal, S., Robertus, C. M., Wang, J., Chan, H., Alamgir, A., & Almonte, J. (2024) · Research Square · doi:10.21203/rs.3.rs-3797623/v1 · Cited by 1 · see citing works
Asokakumar, A., Mathur, B., Chorghade, S., Chau, A., Cronologia, B., Alencastro, F., Wheeler, L., Mathews, C. K., Moore, D. D., Duncan, A. W., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.04.29.651109 · Cited by 1 · see citing works
Self-citationCRISPR/Cas9 gene editing in Huh7 and Hepa RG cell lines
Pâslaru, L., Alexandru, P. R., Creţoiu, S. M., Dima, S., & Popescu, I. (2019) · ROMANIAN BIOTECHNOLOGICAL LETTERS · doi:10.25083/rbl/24.2/216.228
Scott, J., Liu, S., Klatt, K. C., Sun, Z., Guo, Q., Grimm, S. L., Coarfa, C., Dong, B., & Moore, D. D. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.08.08.241661
Self-citationTumors of the Liver in Children
Finegold, M. J., Hadžić, N., & Cho, S. (2021) · Cambridge University Press eBooks · doi:10.1017/9781108918978.042
Self-citationXenobiotic Receptor‐Mediated Gene Regulation in Drug Metabolism and Disposition
Wang, H., & Xie, W. (2022) · Wiley eBooks · doi:10.1002/9781119851042.ch14
Constitutive Androstane Receptor
Yan, J., & Xie, W. (2018) · Elsevier eBooks · doi:10.1016/b978-0-323-95488-4.20028-4
Srivastava, R. K., Singh, P., & Lonard, D. M. (2026) · Biomedicines · doi:10.3390/biomedicines14092046
Tawfik, M. M., Barakat, L. A. A., Elfeky, H. W., & El-Zend, M. A. (2026) · Scientific Reports · doi:10.1038/s41598-026-73629-x
- Authors
- Dong, B., Lee, J.-S., Park, Y.-Y., Yang, F., Xu, G., Huang, W., Finegold, M. J., & Moore, D. D.
- Affiliations
- Baylor College of Medicine (US)
- The University of Texas MD Anderson Cancer Center (US)
- Asan Medical Center (KR)
- City Of Hope National Medical Center (US)
- Corresponding author
- Moore, David D.
- ORCID
- Venue
- Nature Communications
- Published
- 2015-02-09
- Volume
- 6
- Issue
- 1
- Pages
- 5944-5944
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4324535
- OpenAlex
- W2056869677
- Cited by
- 97
- References
- 60
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 8 · 2023: 2 · 2022: 8 · 2021: 8 · 2020: 10 · 2019: 8 · 2018: 16 · 2017: 11 · 2016: 11 · 2015: 5
- FWCI
- 6.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Diana Helis Henry Medical Research Foundation
- National Institutes of Health (NIH-R01)
- University of Texas MD Anderson Cancer Center
- National Cancer Institute (R01CA139158)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK056388, R01DK046546, DK46546, R01 DK46546, DK56388, NIH R01)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Keywords
- hepatocellular carcinoma, β-catenin, hepatocyte proliferation, hepatomegaly, hepatocarcinogenesis, phenobarbital, cellular senescence, growth arrest, gene expression signatures
- MeSH terms
- Constitutive Androstane Receptor, Animals, Disease Models, Animal, Carcinoma, Hepatocellular, Humans, Liver, Liver Neoplasms, Male, Mice, Inbred C57BL, Mutation, Gene Expression Regulation, Neoplastic, Tumor Suppressor Protein p53, Cellular Senescence, Receptors, Cytoplasmic and Nuclear, Gene Expression Profiling, beta Catenin, Carcinogenesis
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
