TCPOBOP‐Induced Hepatomegaly and Hepatocyte Proliferation are Attenuated by Combined Disruption of MET and EGFR Signaling
Open accessAbstract
TCPOBOP (1,4‐Bis [2‐(3,5‐Dichloropyridyloxy)] benzene) is a constitutive androstane receptor (CAR) agonist that induces robust hepatocyte proliferation and hepatomegaly without any liver injury or tissue loss. TCPOBOP‐induced direct hyperplasia has been considered to be CAR‐dependent with no evidence of involvement of cytokines or growth factor signaling. Receptor tyrosine kinases (RTKs), MET and epidermal growth factor receptor (EGFR), are known to play a critical role in liver regeneration after partial hepatectomy, but their role in TCPOBOP‐induced direct hyperplasia, not yet explored, is investigated in the current study. Disruption of the RTK‐mediated signaling was achieved using MET knockout (KO) mice along with Canertinib treatment for EGFR inhibition. Combined elimination of MET and EGFR signaling [MET KO + EGFR inhibitor (EGFRi)], but not individual disruption, dramatically reduced TCPOBOP‐induced hepatomegaly and hepatocyte proliferation. TCPOBOP‐driven CAR activation was not altered in [MET KO + EGFRi] mice, as measured by nuclear CAR translocation and analysis of typical CAR target genes. However, TCPOBOP‐induced cell cycle activation was impaired in [MET KO + EGFRi] mice due to defective induction of cyclins, which regulate cell cycle initiation and progression. TCPOBOP‐driven induction of FOXM1, a key transcriptional regulator of cell cycle progression during TCPOBOP‐mediated hepatocyte proliferation, was greatly attenuated in [MET KO + EGFRi] mice. Interestingly, TCPOBOP treatment caused transient decline in hepatocyte nuclear factor 4 alpha expression concomitant to proliferative response; this was not seen in [MET KO + EGFRi] mice. Transcriptomic profiling revealed the vast majority (~40%) of TCPOBOP‐dependent genes primarily related to proliferative response, but not to drug metabolism, were differentially expressed in [MET KO + EGFRi] mice. Conclusion: Taken together, combined disruption of EGFR and MET signaling lead to dramatic impairment of TCPOBOP‐induced proliferative response without altering CAR activation.
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CAR activation promotes liver growth via MET and EGFR signaling.
“CAR activation also promotes liver growth via the MET proto-oncogene and epidermal growth factor receptor (EGFR) signaling.23”
From Constitutive Androstane Receptor Regulates Bile Acid Homeostasis and Metabolism During Liver Regeneration (2026) · cites this paper as [23]
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Elucidation of a universal size-control mechanism in Drosophila and mammals
Dong, J., Feldmann, G., Huang, J., Wu, S., Zhang, N., Comerford, S. A., Gayyed, M. F., Anders, R. A., Maitra, A., & Pan, D. (2007) · Cell · doi:10.1016/j.cell.2007.07.019 · Cited by 2,370 · see citing works
Michalopoulos, G. K. (2007) · Journal of Cellular Physiology · doi:10.1002/jcp.21172 · Cited by 1,384 · see citing works
Self-citationThe nuclear receptor CAR mediates specific xenobiotic induction of drug metabolism
Wei, P., Zhang, J., Egan-Hafley, M., Liang, S., & Moore, D. D. (2000) · Nature · doi:10.1038/35038112 · Cited by 654 · see citing works
Miao, J., Fang, S., Bae, Y., & Kemper, J. K. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m510713200 · Cited by 197 · see citing works
Suppression of Hepatocyte Proliferation by Hepatocyte Nuclear Factor 4α in Adult Mice
Bonzo, J. A., Ferry, C. H., Matsubara, T., Kim, J.-H., & Gonzalez, F. J. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.334599 · Cited by 193 · see citing works
Liver regeneration versus direct hyperplasia
Columbano, A., & Shinozuka, H. (1996) · The FASEB Journal · doi:10.1096/fasebj.10.10.8751714 · Cited by 188 · 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
Role of Hepatocyte Nuclear Factor 4α (HNF4α) in Cell Proliferation and Cancer
Walesky, C. M., & Apte, U. M. (2015) · Gene Expression · doi:10.3727/105221615x14181438356292 · Cited by 138 · see citing works
Walesky, C. M., Edwards, G., Borude, P. C., Gunewardena, S., O’Neil, M. F., Yoo, B., & Apte, U. M. (2013) · Hepatology · doi:10.1002/hep.26251 · Cited by 130 · see citing works
Paranjpe, S., Bowen, W. C., Mars, W. M., Orr, A., Haynes, M. M., DeFrances, M. C., Liu, S., Tseng, G. C., Tsagianni, A., & Michalopoulos, G. K. (2016) · Hepatology · doi:10.1002/hep.28721 · Cited by 115 · see citing works
Self-citationActivating CAR and β-catenin induces uncontrolled liver growth and tumorigenesis
Dong, B., Lee, J.-S., Park, Y.-Y., Yang, F., Xu, G., Huang, W., Finegold, M. J., & Moore, D. D. (2015) · Nature Communications · doi:10.1038/ncomms6944 · Cited by 97 · see citing works
In vivo hepatocyte proliferation is inducible through a TNF and IL-6-independent pathway
Ledda-Columbano, G. M., Curto, M., Piga, R., Zedda, A. I., Menegazzi, M., Sartori, C., Shinozuka, H., Bluethmann, H., Poli, V, Ciliberto, G., et al. (1998) · Oncogene · doi:10.1038/sj.onc.1202018 · Cited by 96 · see citing works
Ledda-Columbano, G. M., Pibiri, M., Loi, R., Perra, A., Shinozuka, H., & Columbano, A. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64709-8 · Cited by 94 · see citing works
Walesky, C. M., Gunewardena, S., Terwilliger, E. F., Edwards, G., Borude, P. C., & Apte, U. M. (2012) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00064.2012 · Cited by 93 · 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
Kowalik, M. A., Saliba, C., Pibiri, M., Perra, A., Ledda-Columbano, G. M., Sarotto, I., Ghiso, E., Giordano, S., & Columbano, A. (2011) · Hepatology · doi:10.1002/hep.24289 · Cited by 86 · see citing works
Bhushan, B., Chavan, H. D., Borude, P. C., Xie, Y., Du, K., McGill, M. R., Lebofsky, M., Jaeschke, H., Krishnamurthy, P. C., & Apte, U. M. (2016) · Toxicological Sciences · doi:10.1093/toxsci/kfw213 · Cited by 76 · see citing works
Self-citationRoth, A. B., Looser, R., Kaufmann, M., & Meyer, U. (2008) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e3282f706e0 · Cited by 73 · see citing works
López‐Luque, J., Caballero‐Díaz, D., Martinez‐Palacián, A., Roncero, C., Moreno‐Càceres, J., García‐Bravo, M., Grueso, E., Fernández, A., Crosas‐Molist, E., García‐Álvaro, M., et al. (2016) · Hepatology · doi:10.1002/hep.28134 · Cited by 68 · see citing works
Tschuor, C., Kachaylo, E., Limani, P., Raptis, D. A., Linecker, M., Tian, Y., Herrmann, U., Grabliauskaite, K., Weber, A., Columbano, A., et al. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.02.040 · Cited by 68 · see citing works
Gadd45β is an inducible coactivator of transcription that facilitates rapid liver growth in mice
Tian, J., Huang, H., Hoffman‐Liebermann, B., Liebermann, D. A., Ledda‐Columbano, G. M., Columbano, A., & Locker, J. D. (2011) · Journal of Clinical Investigation · doi:10.1172/jci38760 · Cited by 65 · see citing works
T-box transcription factors in cancer biology
Wansleben, S. M., Peres, J., Hare, S., Goding, C. R., & Prince, S. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2014.08.004 · Cited by 63 · see citing works
Columbano, A. (2003) · Carcinogenesis · doi:10.1093/carcin/bgg063 · Cited by 60 · see citing works
Zarrouki, B., Benterki, I., Fontès, G., Peyot, M., Šeda, O., Prentki, M., & Poitout, V. (2013) · Diabetes · doi:10.2337/db13-0425 · Cited by 58 · see citing works
Columbano, A., & Columbano, A. (2003) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401113 · Cited by 54 · see citing works
Shizu, R., Benoki, S., Numakura, Y., Kodama, S., Miyata, M., Yamazoe, Y., & Yoshinari, K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0061802 · Cited by 52 · see citing works
Aging does not reduce the hepatocyte proliferative response of mice to the primary mitogen TCPOBOP
Ledda‐Columbano, G. M., Pibiri, M., Cossu, C., Molotzu, F., Locker, J. D., & Columbano, A. (2004) · Hepatology · doi:10.1002/hep.1840400429 · Cited by 48 · see citing works
Columbano, A., Ledda‐Columbano, G. M., Pibiri, M., Piga, R., Shinozuka, H., Luca, V. D., Cerignoli, F., & Tripodi, M. (1997) · Oncogene · doi:10.1038/sj.onc.1200891 · Cited by 46 · see citing works
The EGF receptor ligand amphiregulin controls cell division via FoxM1
Stoll, S. W., Stuart, P., Swindell, W. R., Tsoi, L. C., Li, B., Gandarillas, A., Lambert, S., Johnston, A., Nair, R. P., & Elder, J. (2015) · Oncogene · doi:10.1038/onc.2015.269 · Cited by 41 · see citing works
Cui, J., Xia, T., Xie, D., Gao, Y., Jia, Z., Wei, D., Wang, L., Huang, S., Quan, M., & Xie, K. (2016) · Oncogene · doi:10.1038/onc.2016.14 · Cited by 41 · 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
The CAR Nuclear Receptor and Hepatocyte Proliferation * #
Costa, R. H., Kalinchenko, V. V., Tan, Y., & Wang, I. (2005) · Hepatology · doi:10.1002/hep.20953 · Cited by 35 · see citing works
Trim24 (Tif1α): An essential ‘brake’ for retinoic acid-induced transcription to prevent liver cancer
Khetchoumian, K., Teletin, M., Tisserand, J., Herquel, B., Ouararhni, K., & Losson, R. (2008) · Cell Cycle · doi:10.4161/cc.7.23.7123 · Cited by 32 · see citing works
LKB1 as a Gatekeeper of Hepatocyte Proliferation and Genomic Integrity during Liver Regeneration
Maillet, V., Boussetta, N., Leclerc, J., Fauveau, V., Foretz, M., Viollet, B., Couty, J., Celton‐Morizur, S., Perret, C., & Desdouets, C. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.01.086 · Cited by 32 · see citing works
Yarushkin, A. A., Качайло, Е. М., & Pustylnyak, V. O. (2012) · British Journal of Pharmacology · doi:10.1111/bph.12090 · Cited by 31 · 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
Francica, P., Nisa, L., Aebersold, D. M., Langer, R., Bladt, F., Blaukat, A., Stroka, D., Martínez, M. R., Zimmer, Y., & Medová, M. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-2987 · Cited by 28 · 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
Kachaylo, E., Yarushkin, A. A., & Pustylnyak, V. O. (2012) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2012.01.007 · Cited by 27 · see citing works
Wang, Y., Zhang, W., Wen, L., Yang, H., Wen, M., Yun, Y., Zhao, L., Zhu, X., Li, T. X., Luo, E., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.11043 · Cited by 19 · see citing works
Leoni, V. P., Ledda‐Columbano, G. M., Pibiri, M., Saliba, C., Perra, A., Kowalik, M. A., Grober, O. M. V., Ravo, M., Weisz, A., Locker, J. D., et al. (2011) · Journal of Hepatology · doi:10.1016/j.jhep.2011.02.016 · Cited by 10 · see citing works
Kanno, Y., Kure, Y., Kobayashi, S., Mizuno, M., Tsuchiya, Y., Yamashita, N., Nemoto, K., & Inouye, Y. (2017) · Drug Metabolism and Disposition · doi:10.1124/dmd.117.077693 · Cited by 3 · see citing works
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Michalopoulos, G. K., & Bhushan, B. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-0342-4 · Cited by 998 · see citing works
Self-citationLiver Regeneration after Acetaminophen Hepatotoxicity
Bhushan, B., & Apte, U. (2019) · The American Journal of Pathology · doi:10.1016/j.ajpath.2018.12.006 · Cited by 179 · see citing works
Self-citationHepatic Stellate Cell Regulation of Liver Regeneration and Repair
Kitto, L. J., & Henderson, N. C. (2020) · Hepatology Communications · doi:10.1002/hep4.1628 · Cited by 117 · see citing works
The xenobiotic receptors PXR and CAR in liver physiology, an update
Cai, X., Young, G. M., & Xie, W. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2021.166101 · Cited by 84 · see citing works
Bhushan, B., & Michalopoulos, G. K. (2020) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2020.109090 · Cited by 66 · see citing works
Self-citationMacrophages harness hepatocyte glutamate to boost liver regeneration
Rigual, M. D. M., Angulo-Aguado, M., Zagorac, S., Álvarez-Díaz, R., Benítez-Mondéjar, M., Yi, F., Martínez-Garay, C., Santos-de-Frutos, K., Kim, E., Campos-Olivas, R., et al. (2025) · Nature · doi:10.1038/s41586-025-08778-6 · Cited by 53 · see citing works
Jiao, T., Yao, X., Zhao, Y.-Y., Zhou, Y., Gao, Y., Fan, S., Chen, P., Li, X., Jiang, Y., Xiao, Y., et al. (2020) · Drug Metabolism and Disposition · doi:10.1124/dmd.120.000061 · Cited by 49 · see citing works
Goldfarb, C. N., Karri, K., Pyatkov, M., & Waxman, D. J. (2022) · Endocrinology · doi:10.1210/endocr/bqac059 · Cited by 46 · see citing works
Kasturi, M., Mathur, V., Gadre, M. A., Srinivasan, V., & Vasanthan, K. S. (2023) · Tissue Engineering and Regenerative Medicine · doi:10.1007/s13770-023-00576-3 · Cited by 44 · see citing works
Gao, Y., Fan, S., Li, H., Jiang, Y., Yao, X., Zhu, S., Yang, X., Wang, R., Tian, J., Gonzalez, F. J., et al. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.11.021 · Cited by 41 · 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
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
Bhushan, B., Gunewardena, S., Edwards, G., & Apte, U. M. (2020) · Food and Chemical Toxicology · doi:10.1016/j.fct.2020.111186 · Cited by 24 · see citing works
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Zhao, P., Fan, S., Gao, Y., Huang, M., & Bi, H. (2022) · Drug Metabolism and Disposition · doi:10.1124/dmd.121.000454 · Cited by 20 · see citing works
Bhushan, B., & Apte, U. M. (2020) · Gene Expression · doi:10.3727/105221620x15901763757677 · Cited by 20 · see citing works
Self-citationBhushan, 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
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
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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
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Hadjittofi, C., Feretis, M., Martin, J. L., Harper, S., & Huguet, E. (2021) · World Journal of Clinical Oncology · doi:10.5306/wjco.v12.i12.1101 · Cited by 18 · 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
Guo, Y., Cui, Q., Ren, S., Hao, D., Morikawa, T., Wang, D., Liu, X., & Pan, Y. (2021) · Journal of Natural Medicines · doi:10.1007/s11418-021-01508-y · Cited by 15 · see citing works
Research on the biological mechanism and potential application of CEMIP
Liu, Y., Hu, G., Li, Y., Kong, X., Yang, K., Li, Z., Lao, W., Li, J., Zhong, J., Zhang, S., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1222425 · Cited by 12 · see citing works
Al-Awadhi, S. S. A., Patil, P., Shetty, P., Shetty, P. K., Shetty, R. A., & Shetty, V. V. (2025) · Bioimpacts · doi:10.34172/bi.30905 · Cited by 11 · see citing works
Scutellaria baicalensis and its flavonoids in the treatment of digestive system tumors
Zhao, K., Zhang, J., Zhou, L., & Sun, Z. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1483785 · Cited by 10 · see citing works
Liu, M., Zhao, X., Wen, J., Sun, L., Huang, R., Zhang, H., Liu, Y., & Ren, X. (2024) · Frontiers in Plant Science · doi:10.3389/fpls.2024.1423678 · Cited by 9 · see citing works
Sonkar, R., Ma, H., & Waxman, D. J. (2024) · Toxicological Sciences · doi:10.1093/toxsci/kfae057 · Cited by 7 · see citing works
Pan, S., Guo, Y., Yu, W., Zhang, J., Qiao, X., Li, L., Xu, P., & Zhai, Y. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032602 · 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
Chen, G., Yang, X.-M., He, Y.-H., Tang, Y.-J., Tian, R.-D., Huang, W., Chen, H., Yang, F., Li, Y., & Lin, S. (2019) · Croatian Medical Journal · doi:10.3325/cmj.2019.60.532 · Cited by 6 · see citing works
Yarushkin, A. A., Mazin, M. E., Pustylnyak, Y. A., Prokopyeva, E. A., & Pustylnyak, V. O. (2019) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2019.108065 · Cited by 6 · see citing works
Tang, X.-H., Liu, Z., Ren, J., Zhang, H., Tian, Y., Hu, J., Sun, Z.-L., & Luo, G. (2025) · Scientific Reports · doi:10.1038/s41598-025-87205-2 · Cited by 5 · see citing works
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Yu, Q., Yu, M., Xie, P., Guo, L., Zhao, Y., Xu, W., Li, X., Wu, M., Zhang, Z., Chen, Z., et al. (2025) · Science Advances · doi:10.1126/sciadv.adw6926 · Cited by 4 · see citing works
Yu, J., Gao, X., Shi, H., Zhang, L., Nie, W., Zhang, R., Fang, M., Liu, Y., Yan, Y., Fan, B., et al. (2025) · Advanced Science · doi:10.1002/advs.202416823 · 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
Self-citationPan, S., Yu, W., Zhang, J., Guo, Y., Qiao, X., Xu, P., & Zhai, Y. (2024) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2024.116061 · Cited by 2 · see citing works
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Self-citationBanerjee, B., Olajide, O. J., Bortolussi, G., & Muro, A. F. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231810703 · Cited by 2 · see citing works
Jain, S., Williams, G., Mukherjee, R., Orr, A. V., Liu, J.-J., Liu, S., Locker, J. D., & Bhushan, B. (2025) · Toxicological Sciences · doi:10.1093/toxsci/kfaf151 · Cited by 1 · see citing works
Self-citationGao, 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
Zhou, W., Chembazhi, U. V., Huang, J., Bangru, S., Dean, A. E., Asokakumar, A., Kalsotra, A., Rudnick, D. A., & Anakk, S. (2026) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2026.101858
Bi, H., Gao, Y., Fan, S., Li, H., Jiang, Y., Yao, X., Zhu, S., Xiao, Y., Wang, R., Tian, J., et al. (2020) · doi:10.22541/au.158817498.80941681
Liu, J., Hu, Y., Du, G., Li, C., Wang, R., Wang, Y., & Dong, J. (2023) · Research Square · doi:10.21203/rs.3.rs-3131364/v1
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Manna, D. F., Laštůvková, H., Schreiberová, J., Jandová, L., Hroch, M., Ambrož, M., Bajnokova, M., Martin Lenicek, A., Hirsova, P., Kacerovský, M., et al. (2026) · Biochemical Pharmacology · doi:10.1016/j.bcp.2026.118397
- Authors
- Bhushan, B., Stoops, J. W., Mars, W. M., Orr, A., Bowen, W. C., Paranjpe, S., & Michalopoulos, G. K.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Michalopoulos, George K.
- Venue
- Hepatology
- Published
- 2018-12-31
- Volume
- 69
- Issue
- 4
- Pages
- 1702-1718
- ISSN
- 0270-9139 (ISSN-L)
- 1527-3350
- PMC
- PMC6289897
- OpenAlex
- W2808462656
- Semantic Scholar
- fde9577ccac24b95bc9f8c14e5e01f6c4f96853b
- Cited by
- 49
- References
- 42
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 7 · 2023: 6 · 2022: 6 · 2021: 4 · 2020: 11 · 2019: 5
- FWCI
- 3.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Natural Science Foundation of China (81670511, 81700501)
- National Institutes of Health (7r01dk083781-14)
- National Cancer Institute (R01CA035373)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 83781, DK78392, DK 64008, R01DK064008, P30DK078392)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Keywords
- TCPOBOP, constitutive androstane receptor, hepatomegaly, hepatocyte proliferation, C-MET signaling, EGFR signaling, receptor tyrosine kinase, canertinib, FOXM1, HNF4α, cyclins, cell cycle regulation
- MeSH terms
- Forkhead Box Protein M1, Hippo Signaling Pathway, Constitutive Androstane Receptor, Animals, Cell Cycle, Female, Hepatomegaly, Pyridines, Signal Transduction, Protein Serine-Threonine Kinases, Receptors, Cytoplasmic and Nuclear, Mice, Knockout, Proto-Oncogene Proteins c-met, Gene Expression Profiling, Hepatocytes, Cell Proliferation, Hepatocyte Nuclear Factor 4, ErbB Receptors
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