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Telomerase can't handle the stress

Telomerase counteracts the telomere shortening that occurs with each round of cell division. In normal human cells, telomerase is repressed, leading to telomere shortening that triggers replicative senescence. However, in most tumors, telomerase is up-regulated and is essential for telomere maintena...

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Detalles Bibliográficos
Autor principal: Smith, Susan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6004074/
https://www.ncbi.nlm.nih.gov/pubmed/29802121
http://dx.doi.org/10.1101/gad.316042.118
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author Smith, Susan
author_facet Smith, Susan
author_sort Smith, Susan
collection PubMed
description Telomerase counteracts the telomere shortening that occurs with each round of cell division. In normal human cells, telomerase is repressed, leading to telomere shortening that triggers replicative senescence. However, in most tumors, telomerase is up-regulated and is essential for telomere maintenance and tumor cell growth. Although long considered a viable target for tumor therapy, successful inhibition of telomerase in cancer therapy remains to be described. In this issue of Genes & Development, Ahmed and Lingner (pp. 658–669) uncover a vulnerability in telomerase upon exposure of cancer cells to oxidative stress. It has long been known that telomeres are sensitive to damage by reactive oxygen species (ROS), but the impact of oxidation on telomerase function in living cells was not known. Using gene knockouts in colon cancer cells, the investigators demonstrate that the antioxidant enzyme peroxiredoxin 1 (PRDX1) and the nudix phosphohydrolase superfamily enzyme (MTH1) cooperate to retain, upon oxidative stress, telomeres in a telomerase-extendible state. Considering that cancer cells are more vulnerable to ROS than noncancer cells, this work may open new avenues targeting telomeres and telomerase in tumor cells.
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spelling pubmed-60040742018-11-01 Telomerase can't handle the stress Smith, Susan Genes Dev Outlook Telomerase counteracts the telomere shortening that occurs with each round of cell division. In normal human cells, telomerase is repressed, leading to telomere shortening that triggers replicative senescence. However, in most tumors, telomerase is up-regulated and is essential for telomere maintenance and tumor cell growth. Although long considered a viable target for tumor therapy, successful inhibition of telomerase in cancer therapy remains to be described. In this issue of Genes & Development, Ahmed and Lingner (pp. 658–669) uncover a vulnerability in telomerase upon exposure of cancer cells to oxidative stress. It has long been known that telomeres are sensitive to damage by reactive oxygen species (ROS), but the impact of oxidation on telomerase function in living cells was not known. Using gene knockouts in colon cancer cells, the investigators demonstrate that the antioxidant enzyme peroxiredoxin 1 (PRDX1) and the nudix phosphohydrolase superfamily enzyme (MTH1) cooperate to retain, upon oxidative stress, telomeres in a telomerase-extendible state. Considering that cancer cells are more vulnerable to ROS than noncancer cells, this work may open new avenues targeting telomeres and telomerase in tumor cells. Cold Spring Harbor Laboratory Press 2018-05-01 /pmc/articles/PMC6004074/ /pubmed/29802121 http://dx.doi.org/10.1101/gad.316042.118 Text en © 2018 Smith; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Outlook
Smith, Susan
Telomerase can't handle the stress
title Telomerase can't handle the stress
title_full Telomerase can't handle the stress
title_fullStr Telomerase can't handle the stress
title_full_unstemmed Telomerase can't handle the stress
title_short Telomerase can't handle the stress
title_sort telomerase can't handle the stress
topic Outlook
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6004074/
https://www.ncbi.nlm.nih.gov/pubmed/29802121
http://dx.doi.org/10.1101/gad.316042.118
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