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Telomere Maintenance and the cGAS-STING Pathway in Cancer

Cancer cells exhibit the unique characteristics of high proliferation and aberrant DNA damage response, which prevents cancer therapy from effectively eliminating them. The machinery required for telomere maintenance, such as telomerase and the alternative lengthening of telomeres (ALT), enables can...

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Autores principales: Ebata, Hiroshi, Loo, Tze Mun, Takahashi, Akiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221635/
https://www.ncbi.nlm.nih.gov/pubmed/35741087
http://dx.doi.org/10.3390/cells11121958
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author Ebata, Hiroshi
Loo, Tze Mun
Takahashi, Akiko
author_facet Ebata, Hiroshi
Loo, Tze Mun
Takahashi, Akiko
author_sort Ebata, Hiroshi
collection PubMed
description Cancer cells exhibit the unique characteristics of high proliferation and aberrant DNA damage response, which prevents cancer therapy from effectively eliminating them. The machinery required for telomere maintenance, such as telomerase and the alternative lengthening of telomeres (ALT), enables cancer cells to proliferate indefinitely. In addition, the molecules in this system are involved in noncanonical pro-tumorigenic functions. Of these, the function of the cyclic GMP–AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, which contains telomere-related molecules, is a well-known contributor to the tumor microenvironment (TME). This review summarizes the current knowledge of the role of telomerase and ALT in cancer regulation, with emphasis on their noncanonical roles beyond telomere maintenance. The components of the cGAS-STING pathway are summarized with respect to intercell communication in the TME. Elucidating the underlying functional connection between telomere-related molecules and TME regulation is important for the development of cancer therapeutics that target cancer-specific pathways in different contexts. Finally, strategies for designing new cancer therapies that target cancer cells and the TME are discussed.
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spelling pubmed-92216352022-06-24 Telomere Maintenance and the cGAS-STING Pathway in Cancer Ebata, Hiroshi Loo, Tze Mun Takahashi, Akiko Cells Review Cancer cells exhibit the unique characteristics of high proliferation and aberrant DNA damage response, which prevents cancer therapy from effectively eliminating them. The machinery required for telomere maintenance, such as telomerase and the alternative lengthening of telomeres (ALT), enables cancer cells to proliferate indefinitely. In addition, the molecules in this system are involved in noncanonical pro-tumorigenic functions. Of these, the function of the cyclic GMP–AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, which contains telomere-related molecules, is a well-known contributor to the tumor microenvironment (TME). This review summarizes the current knowledge of the role of telomerase and ALT in cancer regulation, with emphasis on their noncanonical roles beyond telomere maintenance. The components of the cGAS-STING pathway are summarized with respect to intercell communication in the TME. Elucidating the underlying functional connection between telomere-related molecules and TME regulation is important for the development of cancer therapeutics that target cancer-specific pathways in different contexts. Finally, strategies for designing new cancer therapies that target cancer cells and the TME are discussed. MDPI 2022-06-17 /pmc/articles/PMC9221635/ /pubmed/35741087 http://dx.doi.org/10.3390/cells11121958 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Ebata, Hiroshi
Loo, Tze Mun
Takahashi, Akiko
Telomere Maintenance and the cGAS-STING Pathway in Cancer
title Telomere Maintenance and the cGAS-STING Pathway in Cancer
title_full Telomere Maintenance and the cGAS-STING Pathway in Cancer
title_fullStr Telomere Maintenance and the cGAS-STING Pathway in Cancer
title_full_unstemmed Telomere Maintenance and the cGAS-STING Pathway in Cancer
title_short Telomere Maintenance and the cGAS-STING Pathway in Cancer
title_sort telomere maintenance and the cgas-sting pathway in cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221635/
https://www.ncbi.nlm.nih.gov/pubmed/35741087
http://dx.doi.org/10.3390/cells11121958
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