Telomerase: key regulator of inflammation and cancer.
Author: Wu L1, Fidan K2, Um JY3, Ahn KS4
Affiliation:
1Institute of Molecular and Cell Biology (IMCB), A⁎STAR (Agency for Science, Technology and Research), Singapore 138673, Singapore.
2Institute of Molecular and Cell Biology (IMCB), A⁎STAR (Agency for Science, Technology and Research), Singapore 138673, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore 117597, Singapore.
3College of Korean Medicine, Kyung Hee University, #47, Kyungheedae-gil, Dongdaemoon-gu, Seoul 130-701, Republic of Korea.
4College of Korean Medicine, Kyung Hee University, #47, Kyungheedae-gil, Dongdaemoon-gu, Seoul 130-701, Republic of Korea. Electronic address: ksahn@khu.ac.kr.
Conference/Journal: Pharmacol Res.
Date published: 2020 Feb 25
Other:
Volume ID: 104726 , Special Notes: doi: 10.1016/j.phrs.2020.104726. [Epub ahead of print] , Word Count: 235
The telomerase holoenzyme, which has a highly conserved role in maintaining telomere length, has long been regarded as a high-profile target in cancer therapy due to the high dependency of the majority of cancer cells on constitutive and elevated telomerase activity for sustained proliferation and immortality. In this review, we present the salient findings in the telomerase field with special focus on the association of telomerase with inflammation and cancer. The elucidation of extra-telomeric roles of telomerase in inflammation, reactive oxygen species (ROS) generation, and cancer development further complicated the design of anti-telomerase therapy. Of note, the discovery of the unique mechanism that underlies reactivation of the dormant telomerase reverse transcriptase TERT promoter in somatic cells not only enhanced our understanding of the critical role of TERT in carcinogenesis but also opens up new intervention ideas that enable the differential targeting of cancer cells only. Despite significant effort invested in developing telomerase-targeted therapeutics, devising efficacious cancer-specific telomerase/TERT inhibitors remains an uphill task. The latest discoveries of the telomere-independent functionalities of telomerase in inflammation and cancer can help illuminate the path of developing specific anti-telomerase/TERT therapeutics against cancer cells.
Copyright © 2020. Published by Elsevier Ltd.
KEYWORDS: 2,6-Diaminoanthraquinone(PubChem CID: 8557); 5-Fluorouracil(PubChem CID: 3385); BIBR1532(PubChem CID: 9927531); Cancer; Doxorubicin(PubChem CID: 31703); Imetelstat(PubChem CID: 71587831); Inflammation; MST-312(PubChem CID: 10385095); N-acetyl-L-cysteine(PubChem CID: 12035); NF-κB; ROS; Telomerase; cisplatin(PubChem CID: 5702198); epigallocatechin-3-gallate(PubChem CID: 65064); therapeutics
PMID: 32109579 DOI: 10.1016/j.phrs.2020.104726
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