The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Proliferation of human HCC cells and chemically induced mouse liver cancers requires JNK1-dependent p21 downregulation
Open accessAbstract
JNK proteins have been shown to be involved in liver carcinogenesis in mice, but the extent of their involvement in the development of human liver cancers is unknown. Here, we show that activation of JNK1 but not JNK2 was increased in human primary hepatocellular carcinomas (HCCs). Further, JNK1 was required for human HCC cell proliferation in vitro and tumorigenesis after xenotransplantation. Importantly, mice lacking JNK1 displayed decreased tumor cell proliferation in a mouse model of liver carcinogenesis and decreased hepatocyte proliferation in a mouse model of liver regeneration. In both cases, impaired proliferation was caused by increased expression of p21, a cell-cycle inhibitor, and reduced expression of c-Myc, a negative regulator of p21. Genetic inactivation of p21 in JNK1-/- mice restored hepatocyte proliferation in models of both liver carcinogenesis and liver regeneration, and overexpression of c-Myc increased proliferation of JNK1-/- liver cells. Similarly, JNK1 was found to control the proliferation of human HCC cells by affecting p21 and c-Myc expression. Pharmacologic inhibition of JNK reduced the growth of both xenografted human HCC cells and chemically induced mouse liver cancers. These findings provide a mechanistic link between JNK activity and liver cell proliferation via p21 and c-Myc and suggest JNK targeting can be considered as a new therapeutic approach for HCC treatment.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
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
MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling
Engelman, J. A., Zejnullahu, K., Mitsudomi, T., Song, Y., Hyland, C., Park, J. O., Lindeman, N., Gale, C.-M., Zhao, X., Christensen, J., et al. (2007) · Science · doi:10.1126/science.1141478 · Cited by 4,496
A cytokine-mediated link between innate immunity, inflammation, and cancer
Lin, W.-W., & Karin, M. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31537 · Cited by 1,940
The specificities of protein kinase inhibitors: an update
BAIN, J., McLAUCHLAN, H., ELLIOTT, M., & COHEN, P. (2003) · Biochemical Journal · doi:10.1042/bj20021535 · Cited by 1,369
The JNK signal transduction pathway
Weston, C. R., & Davis, R. J. (2007) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2007.02.001 · Cited by 1,021
Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies
Stommel, J. M., Kimmelman, A. C., Ying, H., Nabioullin, R., Ponugoti, A. H., Wiedemeyer, R., Stegh, A. H., Bradner, J. E., Ligon, K. L., Brennan, C., et al. (2007) · Science · doi:10.1126/science.1142946 · Cited by 938
Kallunki, T., Su, B., Tsigelny, I., Sluss, H. K., Dérijard, B., Moore, G., Davis, R., & Karin, M. (1994) · Genes & Development · doi:10.1101/gad.8.24.2996 · Cited by 642
Stat3-mediated Myc expression is required for Src transformation and PDGF-induced mitogenesis
Bowman, T., Broome, M. A., Sinibaldi, D., Wharton, W., Pledger, W. J., Sedivy, J. M., Irby, R., Yeatman, T., Courtneidge, S. A., & Jove, R. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.131568898 · Cited by 488
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
Wu, H., Wade, M., Krall, L., Grisham, J., Xiong, Y., & Van Dyke, T. (1996) · Genes & Development · doi:10.1101/gad.10.3.245 · Cited by 234
Cited by
Kern, L., Mittenbühler, M., Vesting, A., Ostermann, A., Wunderlich, C., & Wunderlich, F. (2018) · Cancers · doi:10.3390/cancers11010024 · Cited by 331
c-Jun N-terminal kinase (JNK) signaling: Recent advances and challenges
Bogoyevitch, M. A., Ngoei, K. R. W., Zhao, T. T., Yeap, Y. Y. C., & Ng, D. C. H. (2010) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2009.11.002 · Cited by 323
Molecular Signaling Pathways and Therapeutic Targets in Hepatocellular Carcinoma
Dimri, M., & Satyanarayana, A. (2020) · Cancers · doi:10.3390/cancers12020491 · Cited by 311
MAPK signaling in inflammation-associated cancer development
Huang, P., Han, J., & Hui, L. (2010) · Protein & Cell · doi:10.1007/s13238-010-0019-9 · Cited by 273
Self-citationModulation of Hepatic Fibrosis by c-Jun-N-Terminal Kinase Inhibition
Kluwe, J., Pradere, J., Gwak, G., Mencin, A., De Minicis, S., Österreicher, C. H., Colmenero, J., Bataller, R., & Schwabe, R. F. (2010) · Gastroenterology · doi:10.1053/j.gastro.2009.09.015 · Cited by 217
Metadata
- Authors
- Hui, L., Zatloukal, K., Scheuch, H., Stepniak, E., & Wagner, E. F.
- Venue
- Journal of Clinical Investigation
- Published
- 2008-12-01
- Volume
- 118
- Issue
- 12
- Pages
- 3943-3953
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2019953132
- Cited by
- 307
- References
- 11
- FWCI
- 11.64
- Type
- journal article
- Language
- en
- Open access
- green
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
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Proliferation of human HCC cells and chemically induced mouse liver cancers requires JNK1-dependent p21 downregulation. https://app.cochat.ai/papers/10.1172/jci37156
- The paper
- Hui, L., Zatloukal, K., Scheuch, H., Stepniak, E., & Wagner, E. F. (2008). Proliferation of human HCC cells and chemically induced mouse liver cancers requires JNK1-dependent p21 downregulation. Journal of Clinical Investigation. https://doi.org/10.1172/jci37156
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
