Inhibiting TRF1 upstream signaling pathways to target telomeres in cancer cells

Abstract In the context of tumorigenesis, telomere shortening is associated with apparent antagonistic outcomes: On one side, it favors cancer initiation through mechanisms involving genome instability, while on the other side, it prevents cancer progression, due to the activation of the DNA damage...

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Main Authors: Julien Cherfils‐Vicini, Eric Gilson
Format: Article
Language:English
Published: Springer Nature 2019-06-01
Series:EMBO Molecular Medicine
Online Access:https://doi.org/10.15252/emmm.201910845
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author Julien Cherfils‐Vicini
Eric Gilson
author_facet Julien Cherfils‐Vicini
Eric Gilson
author_sort Julien Cherfils‐Vicini
collection DOAJ
description Abstract In the context of tumorigenesis, telomere shortening is associated with apparent antagonistic outcomes: On one side, it favors cancer initiation through mechanisms involving genome instability, while on the other side, it prevents cancer progression, due to the activation of the DNA damage response (DDR) checkpoint behaving as a cell‐intrinsic proliferation barrier. Consequently, telomerase, which can compensate for replicative erosion by adding telomeric DNA repeats at the chromosomal DNA extremities, is crucial for cancer progression and is upregulated in nearly 90% of human cancers. Therefore, telomeres are considered potential anti‐cancer targets and, to date, most of the studies have focused on telomerase inhibition. However, the development of clinically efficient telomerase targeting therapies is still in its infancy. In this context, the findings reported in this issue of EMBO Molecular Medicine by Bejarano et al (2019) open new avenues for alternative telomere therapies.
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spelling doaj-art-8c50f1904e294cff8fe89299ee0fc6e82025-08-20T03:43:14ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842019-06-011171210.15252/emmm.201910845Inhibiting TRF1 upstream signaling pathways to target telomeres in cancer cellsJulien Cherfils‐Vicini0Eric Gilson1Université Côte d'Azur (UCA), Centre National de la Recherche Scientifique (CNRS) UMR7284, Institut National de la Santé et de la Recherche Médicale (INSERM) U1081, Institute for Research on Cancer and AgingUniversité Côte d'Azur (UCA), Centre National de la Recherche Scientifique (CNRS) UMR7284, Institut National de la Santé et de la Recherche Médicale (INSERM) U1081, Institute for Research on Cancer and AgingAbstract In the context of tumorigenesis, telomere shortening is associated with apparent antagonistic outcomes: On one side, it favors cancer initiation through mechanisms involving genome instability, while on the other side, it prevents cancer progression, due to the activation of the DNA damage response (DDR) checkpoint behaving as a cell‐intrinsic proliferation barrier. Consequently, telomerase, which can compensate for replicative erosion by adding telomeric DNA repeats at the chromosomal DNA extremities, is crucial for cancer progression and is upregulated in nearly 90% of human cancers. Therefore, telomeres are considered potential anti‐cancer targets and, to date, most of the studies have focused on telomerase inhibition. However, the development of clinically efficient telomerase targeting therapies is still in its infancy. In this context, the findings reported in this issue of EMBO Molecular Medicine by Bejarano et al (2019) open new avenues for alternative telomere therapies.https://doi.org/10.15252/emmm.201910845
spellingShingle Julien Cherfils‐Vicini
Eric Gilson
Inhibiting TRF1 upstream signaling pathways to target telomeres in cancer cells
EMBO Molecular Medicine
title Inhibiting TRF1 upstream signaling pathways to target telomeres in cancer cells
title_full Inhibiting TRF1 upstream signaling pathways to target telomeres in cancer cells
title_fullStr Inhibiting TRF1 upstream signaling pathways to target telomeres in cancer cells
title_full_unstemmed Inhibiting TRF1 upstream signaling pathways to target telomeres in cancer cells
title_short Inhibiting TRF1 upstream signaling pathways to target telomeres in cancer cells
title_sort inhibiting trf1 upstream signaling pathways to target telomeres in cancer cells
url https://doi.org/10.15252/emmm.201910845
work_keys_str_mv AT juliencherfilsvicini inhibitingtrf1upstreamsignalingpathwaystotargettelomeresincancercells
AT ericgilson inhibitingtrf1upstreamsignalingpathwaystotargettelomeresincancercells