Evidence map›Paper›PMID 29097657›Full record

ArticleNature communications2017

Modulation of telomere protection by the PI3K/AKT pathway.

Marinela Méndez-Pertuz, Paula Martínez, Carmen Blanco-Aparicio, Elena Gómez-Casero, Ana Belen García, Jorge Martínez-Torrecuadrada, Marta Palafox, Javier Cortés, Violeta Serra, Joaquin Pastor and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 1 pooled it
3.7field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

43 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.

  1. Pooled it
  2. Vitamin DThe American journal of clinical nutrition · 2025
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  16. Ginsenoside F1-Mediated Telomere Preservation Delays Cellular Senescence.International journal of molecular sciences · 2023
    Article
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  19. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Marinela Méndez-PertuzTelomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3, Madrid, E-28029, Spain.
Paula MartínezTelomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3, Madrid, E-28029, Spain.
Carmen Blanco-AparicioExperimental Therapeutics Program, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3, Madrid, E-28029, Spain.
Elena Gómez-CaseroExperimental Therapeutics Program, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3, Madrid, E-28029, Spain.
Ana Belen GarcíaExperimental Therapeutics Program, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3, Madrid, E-28029, Spain.
Jorge Martínez-TorrecuadradaBiotechnology Program, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3, Madrid, E-28029, Spain.
Marta PalafoxExperimental Therapeutics Group, Vall d´Hebron Institute of Oncology (VHIO), Natzaret 115-117, Barcelona, E-08035, Spain.
Javier CortésExperimental Therapeutics Group, Vall d´Hebron Institute of Oncology (VHIO), Natzaret 115-117, Barcelona, E-08035, Spain.
Violeta SerraExperimental Therapeutics Group, Vall d´Hebron Institute of Oncology (VHIO), Natzaret 115-117, Barcelona, E-08035, Spain.
Joaquin PastorExperimental Therapeutics Program, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3, Madrid, E-28029, Spain.
Maria A BlascoTelomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3, Madrid, E-28029, Spain. mblasco@cnio.es.
Spanish National Cancer Research Centre · ESVall d'Hebron Institute of Oncology

Funding

Worldwide Cancer Research 16-1177
6 · The paper itself

Abstract

Telomeres and the insulin/PI3K pathway are considered hallmarks of aging and cancer. Here, we describe a role for PI3K/AKT in the regulation of TRF1, an essential component of the shelterin complex. PI3K and AKT chemical inhibitors reduce TRF1 telomeric foci and lead to increased telomeric DNA damage and fragility. We identify the PI3Kα isoform as responsible for this TRF1 inhibition. TRF1 is phosphorylated at different residues by AKT and these modifications regulate TRF1 protein stability and TRF1 binding to telomeric DNA in vitro and are important for in vivo TRF1 telomere location and cell viability. Patient-derived breast cancer PDX mouse models that effectively respond to a PI3Kα specific inhibitor, BYL719, show decreased TRF1 levels and increased DNA damage. These findings functionally connect two of the major pathways for cancer and aging, telomeres and the PI3K pathway, and pinpoint PI3K and AKT as novel targets for chemical modulation of telomere protection.

Indexed as

AgingAnimalsBreast NeoplasmsClass I Phosphatidylinositol 3-KinasesDNA DamageHumansMiceNeoplasm TransplantationPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphorylationProtein StabilityProto-Oncogene Proteins c-aktTelomereTelomeric Repeat Binding Protein 1ThiazolesAlpelisibClass I Phosphatidylinositol 3-KinasesPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPik3ca protein, mouseProto-Oncogene Proteins c-aktTelomeric Repeat Binding Protein 1Thiazoles

Identifiers

PMID29097657
PMCPMC5668434
OpenAlexW2765122346

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.