Cited by 378Telomeres, Telomerase, and SenescenceNF-κB Signaling PathwaysTGF-β signaling in diseases

Telomerase directly regulates NF-κB-dependent transcription

Ghosh, Arkasubhra, Saginc, Gaye, Leow, Shi Chi, Khattar, Ekta, Shin, Eun Myong, Yan, Ting Dong, Wong, Marc, Zhang, Zhizhuo +7 more·2012·Nature Cell Biology

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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Crossref · 10.1038/ncb2621

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  • Apart from initiating replicative immortality, telomerase seems to play a crucial role in almost all the hallmarks of cancer, including cell growth and proliferation through activation of EGFR signaling, resistance to apoptosis through activation of NF-kB, promotion of invasion and metastasis through induction of epithelial-mesenchymal transition via the Wnt/b-catenin pathway that upregulates Snai

    “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”

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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
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
Locations
  • Nature Cell Biology (publishedVersion)
  • PubMed (publishedVersion)
  • National University of Singapore (submittedVersion)
Funders
Agency for Science, Technology and Research
Topics
  • Health Sciences › Medicine › Physiology › 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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