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Published on: January 12, 2020
Telomerase directly regulates NF-κB-dependent transcription
Arkasubhra Ghosh1, Gaye Saginc, Shi Chi Leow
1Laboratory of NFκB Signaling, IMCB, Proteos, 138673, Singapore.
Telomerase, crucial for cancer cell growth, also regulates inflammation via NF-κB. This study reveals a feedback loop where telomerase controls NF-κB, which in turn boosts telomerase, driving cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Reactivated telomerase is vital for cancer cell immortality, but its roles extend beyond telomere elongation.
- Nuclear factor kappa B (NF-κB) is a key regulator of inflammation and cellular processes implicated in cancer.
Purpose of the Study:
- To investigate the interplay between telomerase and NF-κB signaling in human cancer cells.
- To elucidate the molecular mechanisms underlying the functional relationship between telomerase and NF-κB.
Main Methods:
- Investigated the effects of modulating NF-κB signaling on telomerase activity and cancer-relevant processes.
- Examined telomerase binding to NF-κB subunits and its recruitment to specific gene promoters.
- Assessed the impact of NF-κB on telomerase gene expression.
Main Results:
- Blocking NF-κB signaling inhibited telomerase overexpression effects on transformation-related processes.
- Enhanced NF-κB activity could compensate for reduced telomerase activity.
- Telomerase directly binds to NF-κB p65 and regulates expression of inflammatory cytokines like IL-6 and TNF-α.
- NF-κB was found to transcriptionally upregulate telomerase levels.
Conclusions:
- A feed-forward regulatory loop exists between telomerase and NF-κB, contributing to chronic inflammation and sustained telomerase activity in cancers.
- This interplay offers potential therapeutic targets for cancer treatment by disrupting the link between inflammation and cancer cell maintenance.
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