ArticleEMBO molecular medicine2019
Multiple cancer pathways regulate telomere protection.
Article in EMBO molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 56 citations in OpenAlex.
- CDK2-mediated phosphorylation of TRF1 S11 facilitates DNA damage repair by remodeling telomeric chromatin.Cell death and differentiation · 2026Article
- Quantifying telomere length: from bulk assays to single-molecule resolution.Biophysics reports · 2026Article
- Article
- Targeting telomeres in brain vasculature does not impede initiation and progression of glioblastoma.PloS one · 2026Article
- Discovery of first-in-class inhibitors of the TRF1:TIN2 protein:protein interaction by fragment screening.Scientific reports · 2025Article
- Depletion of the TRF1 telomere-binding protein leads to leaner mice with altered metabolic profiles.Aging · 2025Article
- Evaluating the Effect of Telomere Length on Oral and Oropharyngeal Cancer Risk Using Mendelian Randomization.International dental journal · 2025Article
- A Narrative Review of Prognostic Gene Signatures in Oral Squamous Cell Carcinoma Using LASSO Cox Regression.Biomedicines · 2025Review
- Targeting telomere dynamics with plant-derived compounds: Molecular strategies against aging.Current research in pharmacology and drug discovery · 2025Review
- Novel role for Ddx39 in differentiation and telomere length regulation of embryonic stem cells.Cell death and differentiation · 2024Article
- As a novel prognostic model for breast cancer, the identification and validation of telomere-related long noncoding RNA signatures.World journal of surgical oncology · 2024Article
- The Role of Glia Telomere Dysfunction in the Pathogenesis of Central Nervous System Diseases.Molecular neurobiology · 2024Review
- Differential contribution for ERK1 and ERK2 kinases in BRAFCell death and differentiation · 2024Article
- Unlocking longevity: the role of telomeres and its targeting interventions.Frontiers in aging · 2024Review
- ERCC4: a potential regulatory factor in inflammatory bowel disease and inflammation-associated colorectal cancer.Frontiers in endocrinology · 2024Review
- Inhibition of demethylase by IOX1 modulates chromatin accessibility to enhance NSCLC radiation sensitivity through attenuated PIF1.Cell death & disease · 2023Article
- Drug repositioning strategy for the identification of novel telomere-damaging agents: A role for NAMPT inhibitors.Aging cell · 2023Article
- R-Loops and R-Loop-Binding Proteins in Cancer Progression and Drug Resistance.International journal of molecular sciences · 2023Review
- Signalling inhibition by ponatinib disrupts productive alternative lengthening of telomeres (ALT).Nature communications · 2023Article
- The Molecular Mechanisms and Therapeutic Prospects of Alternative Lengthening of Telomeres (ALT).Cancers · 2023Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Telomeres are considered as universal anti-cancer targets, as telomere maintenance is essential to sustain indefinite cancer growth. Mutations in telomerase, the enzyme that maintains telomeres, are among the most frequently found in cancer. In addition, mutations in components of the telomere protective complex, or shelterin, are also found in familial and sporadic cancers. Most efforts to target telomeres have focused in telomerase inhibition; however, recent studies suggest that direct targeting of the shelterin complex could represent a more effective strategy. In particular, we recently showed that genetic deletion of the TRF1 essential shelterin protein impairs tumor growth in aggressive lung cancer and glioblastoma (GBM) mouse models by direct induction of telomere damage independently of telomere length. Here, we screen for TRF1 inhibitory drugs using a collection of FDA-approved drugs and drugs in clinical trials, which cover the majority of pathways included in the Reactome database. Among other targets, we find that inhibition of several kinases of the Ras pathway, including ERK and MEK, recapitulates the effects of Trf1 genetic deletion, including induction of telomeric DNA damage, telomere fragility, and inhibition of cancer stemness. We further show that both bRAF and ERK2 kinases phosphorylate TRF1 in vitro and that these modifications are essential for TRF1 location to telomeres in vivo. Finally, we use these new TRF1 regulatory pathways as the basis to discover novel drug combinations based on TRF1 inhibition, with the goal of effectively blocking potential resistance to individual drugs in patient-derived glioblastoma xenograft models.
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Registered trials
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.