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Non-canonical roles of canonical telomere binding proteins in cancers

Reactivation of telomerase is a major hallmark observed in 90% of all cancers. Yet paradoxically, enhanced telomerase activity does not correlate with telomere length and cancers often possess short telomeres; suggestive of supplementary non-canonical roles that telomerase might play in the developm...

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Autores principales: Akincilar, Semih Can, Chan, Claire Hian Tzer, Ng, Qin Feng, Fidan, Kerem, Tergaonkar, Vinay
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164586/
https://www.ncbi.nlm.nih.gov/pubmed/33599797
http://dx.doi.org/10.1007/s00018-021-03783-0
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author Akincilar, Semih Can
Chan, Claire Hian Tzer
Ng, Qin Feng
Fidan, Kerem
Tergaonkar, Vinay
author_facet Akincilar, Semih Can
Chan, Claire Hian Tzer
Ng, Qin Feng
Fidan, Kerem
Tergaonkar, Vinay
author_sort Akincilar, Semih Can
collection PubMed
description Reactivation of telomerase is a major hallmark observed in 90% of all cancers. Yet paradoxically, enhanced telomerase activity does not correlate with telomere length and cancers often possess short telomeres; suggestive of supplementary non-canonical roles that telomerase might play in the development of cancer. Moreover, studies have shown that aberrant expression of shelterin proteins coupled with their release from shortening telomeres can further promote cancer by mechanisms independent of their telomeric role. While targeting telomerase activity appears to be an attractive therapeutic option, this approach has failed in clinical trials due to undesirable cytotoxic effects on stem cells. To circumvent this concern, an alternative strategy could be to target the molecules involved in the non-canonical functions of telomeric proteins. In this review, we will focus on emerging evidence that has demonstrated the non-canonical roles of telomeric proteins and their impact on tumorigenesis. Furthermore, we aim to address current knowledge gaps in telomeric protein functions and propose future research approaches that can be undertaken to achieve this.
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spelling pubmed-81645862021-06-17 Non-canonical roles of canonical telomere binding proteins in cancers Akincilar, Semih Can Chan, Claire Hian Tzer Ng, Qin Feng Fidan, Kerem Tergaonkar, Vinay Cell Mol Life Sci Review Reactivation of telomerase is a major hallmark observed in 90% of all cancers. Yet paradoxically, enhanced telomerase activity does not correlate with telomere length and cancers often possess short telomeres; suggestive of supplementary non-canonical roles that telomerase might play in the development of cancer. Moreover, studies have shown that aberrant expression of shelterin proteins coupled with their release from shortening telomeres can further promote cancer by mechanisms independent of their telomeric role. While targeting telomerase activity appears to be an attractive therapeutic option, this approach has failed in clinical trials due to undesirable cytotoxic effects on stem cells. To circumvent this concern, an alternative strategy could be to target the molecules involved in the non-canonical functions of telomeric proteins. In this review, we will focus on emerging evidence that has demonstrated the non-canonical roles of telomeric proteins and their impact on tumorigenesis. Furthermore, we aim to address current knowledge gaps in telomeric protein functions and propose future research approaches that can be undertaken to achieve this. Springer International Publishing 2021-02-18 2021 /pmc/articles/PMC8164586/ /pubmed/33599797 http://dx.doi.org/10.1007/s00018-021-03783-0 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Review
Akincilar, Semih Can
Chan, Claire Hian Tzer
Ng, Qin Feng
Fidan, Kerem
Tergaonkar, Vinay
Non-canonical roles of canonical telomere binding proteins in cancers
title Non-canonical roles of canonical telomere binding proteins in cancers
title_full Non-canonical roles of canonical telomere binding proteins in cancers
title_fullStr Non-canonical roles of canonical telomere binding proteins in cancers
title_full_unstemmed Non-canonical roles of canonical telomere binding proteins in cancers
title_short Non-canonical roles of canonical telomere binding proteins in cancers
title_sort non-canonical roles of canonical telomere binding proteins in cancers
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164586/
https://www.ncbi.nlm.nih.gov/pubmed/33599797
http://dx.doi.org/10.1007/s00018-021-03783-0
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