2026-04-29T01:00:09Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/83152024-11-30T00:46:54Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Bejarano, Leire
author
Louzame, Jessica
author
Montero, Juán José
author
Megias Vazquez, Diego
author
Flores, Juana M
author
Blasco , MA
funder
Ministerio de Economía y Competitividad (España)
funder
Botín Foundation
funder
Fundación La Caixa
funder
Banco Santander
funder
Worldwide Cancer Research
2019-08-27T12:29:51Z
2019-08-27T12:29:51Z
2019-08-08
iScience. 2019;19:572-585
25890042
http://hdl.handle.net/20.500.12105/8315
31446222
10.1016/j.isci.2019.08.012
2589-0042
iScience
Telomeres are considered potential anti-cancer targets. Most studies have focused on telomerase inhibition, but this strategy has largely failed in clinical trials. Direct disruption of the shelterin complex through TRF1 inhibition can block tumorigenesis in cancer mouse models by a mechanism that involves DNA damage induction and reduction of proliferation and stemness. Any anti-cancer target, however, must fulfill the requisite of not showing deleterious effects in healthy tissues. Here, we show that Trf1 genetic deletion in wild-type and cancer-prone p53- and Ink4Arf-deficient mice does not affect organismal viability and only induces mild phenotypes like decreased body weight and hair graying or hair loss, the skin being the most affected tissue. Importantly, we found that Trf1 is essential for tumorigenesis in p53- and Ink4Arf-deficient mice, as we did not find a single tumor originating from Trf1-deleted cells. These findings indicate a therapeutic window for targeting Trf1 in cancer treatment.
eng
Cancer
Model Organism
Safety Assessment
Safety of Whole-Body Abrogation of the TRF1 Shelterin Protein in Wild-Type and Cancer-Prone Mouse Models
journal article
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URL
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SafetyofWhole-BodyAbrogation_2019.pdf
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SafetyofWhole-BodyAbrogation_2019_suplementary.pdf
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SafetyofWhole-BodyAbrogation_2019.pdf.txt
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