The DOI matches its Crossref record; 70 of the 70 references it cites were found in a registry or an index.
Telomerase directly regulates NF-κB-dependent transcription
Abstract
Although elongation of telomeres is thought to be the prime function of reactivated telomerase in cancers, this activity alone does not account for all of the properties that telomerase reactivation attributes to human cancer cells. Here, we uncover a link between telomerase and NF-κB, a master regulator of inflammation. We observe that while blocking NF-κB signalling can inhibit effects of telomerase overexpression on processes relevant to transformation, increasing NF-κB activity can functionally substitute for reduced telomerase activity. Telomerase directly regulates NF-κB-dependent gene expression by binding to the NF-κB p65 subunit and recruitment to a subset of NF-κB promoters such as those of IL-6 and TNF-α, cytokines that are critical for inflammation and cancer progression. As NF-κB can transcriptionally upregulate telomerase levels, our findings suggest that a feed-forward regulation between them could be the key mechanistic basis for the coexistence of chronic inflammation and sustained telomerase activity in human cancers.
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“It has to be noted though that apart from initiating replicative immortality, telomerase seems to play a crucial role in almost all the hallmarks of cancer, ranging from cell growth and proliferation through to the activation of EGFR signaling [182], resistance to apoptosis through activation of NF-kB [183], and the promotion of invasion and metastasis through induction of the epithelial–mesenchym”
From Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy (2024) · cites this paper as [183]
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Chronic inflammation induces telomere dysfunction and accelerates ageing in mice
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Metadata
- Authors
- Ghosh, A., Saginc, G., Leow, S. C., Khattar, E., Shin, E. M., Yan, T. D., Wong, M., Zhang, Z., Li, G., Sung, W.-K., Zhou, J., Chng, W. J., Li, S., Liu, E., & Tergaonkar, V.
- Affiliations
- Institute of Molecular and Cell Biology (SG)
- Genome Institute of Singapore (SG)
- National University of Singapore (SG)
- Cancer Science Institute of Singapore (SG)
- Corresponding author
- Tergaonkar, Vinay
- ORCID
- Venue
- Nature Cell Biology
- Published
- 2012-11-18
- Volume
- 14
- Issue
- 12
- Pages
- 1270-1281
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2033861401
- Cited by
- 378
- References
- 70
- Citations by year
- 2026: 20 · 2025: 27 · 2024: 27 · 2023: 34 · 2022: 29 · 2021: 30 · 2020: 32 · 2019: 22 · 2018: 28 · 2017: 19 · 2016: 33 · 2015: 48 · 2014: 15 · 2013: 14
- FWCI
- 16.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion)
- Funders
- Agency for Science, Technology and Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- telomerase, NF-κB, NF-κB p65, transcriptional regulation, telomere elongation, chronic inflammation, tumor progression, interleukin-6, TNF-α, feedforward control, telomerase reactivation, tumor inflammation
- MeSH terms
- Animals, Female, Humans, Male, Promoter Regions, Genetic, Transcription, Genetic, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha, Signal Transduction, Interleukin-6, NF-kappa B, Telomerase, Cell Line, Tumor, Mice
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