The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Crosstalk between the canonical NF-κB and Notch signaling pathways inhibits Pparγ expression and promotes pancreatic cancer progression in mice
Open accessAbstract
The majority of human pancreatic cancers have activating mutations in the KRAS proto-oncogene. These mutations result in increased activity of the NF-κB pathway and the subsequent constitutive production of proinflammatory cytokines. Here, we show that inhibitor of κB kinase 2 (Ikk2), a component of the canonical NF-κB signaling pathway, synergizes with basal Notch signaling to upregulate transcription of primary Notch target genes, resulting in suppression of antiinflammatory protein expression and promotion of pancreatic carcinogenesis in mice. We found that in the Kras(G12D)Pdx1-cre mouse model of pancreatic cancer, genetic deletion of Ikk2 in initiated pre-malignant epithelial cells substantially delayed pancreatic oncogenesis and resulted in downregulation of the classical Notch target genes Hes1 and Hey1. Tnf-α stimulated canonical NF-κB signaling and, in collaboration with basal Notch signals, induced optimal expression of Notch targets. Mechanistically, Tnf-α stimulation resulted in phosphorylation of histone H3 at the Hes1 promoter, and this signal was lost with Ikk2 deletion. Hes1 suppresses expression of Pparg, which encodes the antiinflammatory nuclear receptor Pparγ. Thus, crosstalk between Tnf-α/Ikk2 and Notch sustains the intrinsic inflammatory profile of transformed cells. These findings reveal what we believe to be a novel interaction between oncogenic inflammation and a major cell fate pathway and show how these pathways can cooperate to promote cancer progression.
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
Mantovani, A., Allavena, P., Sica, A., & Balkwill, F. (2008) · Nature · doi:10.1038/nature07205 · Cited by 11,399
Self-citationIKKβ Links Inflammation and Tumorigenesis in a Mouse Model of Colitis-Associated Cancer
Greten, F. R., Eckmann, L., Greten, T. F., Park, J. M., Li, Z.-W., Egan, L. J., Kagnoff, M. F., & Karin, M. (2004) · Cell · doi:10.1016/j.cell.2004.07.013 · Cited by 2,433
Metformin and reduced risk of cancer in diabetic patients
Evans, J. M. M., Donnelly, L. A., Emslie-Smith, A. M., Alessi, D. R., & Morris, A. D. (2005) · BMJ · doi:10.1136/bmj.38415.708634.f7 · Cited by 2,388
The influence of glucose-lowering therapies on cancer risk in type 2 diabetes
Currie, C. J., Poole, C. D., & Gale, E. A. M. (2009) · Diabetologia · doi:10.1007/s00125-009-1440-6 · Cited by 1,124
Dynamics of the immune reaction to pancreatic cancer from inception to invasion
Clark, C. E., Hingorani, S. R., Mick, R., Combs, C., Tuveson, D. A., & Vonderheide, R. H. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-0175 · Cited by 990
Self-citationMice deficient in tumor necrosis factor-α are resistant to skin carcinogenesis
Moore, R. J., Owens, D. M., Stamp, G., Arnott, C., Burke, F., East, N., Holdsworth, H., Turner, L., Rollins, B., Pasparakis, M., et al. (1999) · Nature Medicine · doi:10.1038/10552 · Cited by 839
Self-citation“Re-educating” tumor-associated macrophages by targeting NF-κB
Hagemann, T., Lawrence, T., McNeish, I., Charles, K. A., Kulbe, H., Thompson, R. G., Robinson, S. C., & Balkwill, F. R. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20080108 · Cited by 792
Self-citationNotch mediates TGFα-induced changes in epithelial differentiation during pancreatic tumorigenesis
Miyamoto, Y., Maitra, A., Ghosh, B., Zechner, U., Argani, P., Iacobuzio-Donahue, C. A., Sriuranpong, V., Iso, T., Meszoely, I. M., Wolfe, M. S., et al. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00140-5 · Cited by 643
Nuclear receptor transrepression pathways that regulate inflammation in macrophages and T cells
Glass, C. K., & Saijo, K. (2010) · Nature Reviews Immunology · doi:10.1038/nri2748 · Cited by 619
Requirement of the NF-κB Subunit p65/RelA for K-Ras–Induced Lung Tumorigenesis
Bassères, D. S., Ebbs, A., Levantini, E., & Baldwin, A. S. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-4290 · Cited by 189
Cited by
Mantovani, A., Allavena, P., Sica, A., & Balkwill, F. (2008) · Nature · doi:10.1038/nature07205 · Cited by 11,399
Self-citationNF-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
Notch signaling pathway: architecture, disease, and therapeutics
Zhou, B., Lin, W., Long, Y., Yang, Y., Zhang, H., Wu, K., & Chu, Q. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00934-y · Cited by 1,114
Steele, C. W., Karim, S. A., Leach, J. D. G., Bailey, P., Upstill-Goddard, R., Rishi, L., Foth, M., Bryson, S., McDaid, K., Wilson, Z., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.04.014 · Cited by 845
Self-citationAcinar cell plasticity and development of pancreatic ductal adenocarcinoma
Storz, P. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2017.12 · Cited by 389
Metadata
- Authors
- Maniati, E., Bossard, M., Cook, N., Candido, J. B., Emami-Shahri, N., Nedospasov, S. A., Balkwill, F. R., Tuveson, D. A., & Hagemann, T.
- Venue
- Journal of Clinical Investigation
- Published
- 2011-12-01
- Volume
- 121
- Issue
- 12
- Pages
- 4685-4699
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2098517576
- Cited by
- 248
- References
- 10
- FWCI
- 5.40
- 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: Crosstalk between the canonical NF-κB and Notch signaling pathways inhibits Pparγ expression and promotes pancreatic cancer progression in mice. https://app.cochat.ai/papers/10.1172/jci45797
- The paper
- Maniati, E., Bossard, M., Cook, N., Candido, J. B., Emami-Shahri, N., Nedospasov, S. A., Balkwill, F. R., Tuveson, D. A., & Hagemann, T. (2011). Crosstalk between the canonical NF-κB and Notch signaling pathways inhibits Pparγ expression and promotes pancreatic cancer progression in mice. Journal of Clinical Investigation. https://doi.org/10.1172/jci45797
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.
