ArticleGenes2020
G-quadruplex Stabilization Fuels the ALT Pathway in ALT-positive Osteosarcoma Cells.
Article in Genes, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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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.
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.
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Who cites it
34 citing papers in PubMed, 49 citations in OpenAlex.
- G quadruplex DNA facilitates a pervasive path to homologous recombination.bioRxiv : the preprint server for biology · 2026Article
- Repurposing MK0873 as a non-covalent hTERT-Targeting compound: a proof of concept study.Frontiers in aging · 2026Article
- The alternative lengthening of telomeres pathway through a DNA repair lens: mechanism and therapeutic opportunities.NAR cancer · 2025Review
- Modulating TERRA G-quadruplexes with ligands: impact on telomeric DNA:RNA hybrids and ALT mechanisms.Nucleic acids research · 2025Article
- Atypical R-loops in cancer: decoding molecular chaos for therapeutic gain.Journal of translational medicine · 2025Review
- Cellular adaptations impact the biological activity of naphthalene diimide G-quadruplex ligands in ALT-positive osteosarcoma cells.Cell death & disease · 2025Article
- Biomolecular Condensates in Telomere Maintenance of ALT Cancer Cells.Journal of molecular biology · 2025Review
- Locking the gates of immortality: targeting alternative lengthening of telomeres (ALT) pathways.Medical oncology (Northwood, London, England) · 2025Review
- Polyubiquitinated PCNA triggers SLX4-mediated break-induced replication in alternative lengthening of telomeres (ALT) cancer cells.Nucleic acids research · 2024Article
- HLTF resolves G4s and promotes G4-induced replication fork slowing to maintain genome stability.Molecular cell · 2024Article
- Therapeutic Use of G4-Ligands in Cancer: State-of-the-Art and Future Perspectives.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Bioactive nutraceuticals as G4 stabilizers: potential cancer prevention and therapy-a critical review.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- BG4 antibody can recognize telomeric G-quadruplexes harboring destabilizing base modifications and lesions.Nucleic acids research · 2024Article
- Oxidative guanine base damage plays a dual role in regulating productive ALT-associated homology-directed repair.Cell reports · 2024Article
- Genome maintenance meets mechanobiology.Chromosoma · 2024Review
- Telomeres and telomerase in Sarcoma disease and therapy.International journal of medical sciences · 2024Review
- Combining old and new concepts in targeting telomerase for cancer therapy: transient, immediate, complete and combinatory attack (TICCA).Cancer cell international · 2023Review
- The Molecular Mechanisms and Therapeutic Prospects of Alternative Lengthening of Telomeres (ALT).Cancers · 2023Review
- Crosstalk between G-quadruplex and ROS.Cell death & disease · 2023Review
- Telomeres expand sphere of influence: emerging molecular impact of telomeres in non-telomeric functions.Trends in genetics : TIG · 2023Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most human tumors maintain telomere lengths by telomerase, whereas a portion of them (10%-15%) uses a mechanism named alternative lengthening of telomeres (ALT). The telomeric G-quadruplex (G4) ligand RHPS4 is known for its potent antiproliferative effect, as shown in telomerase-positive cancer models. Moreover, RHPS4 is also able to reduce cell proliferation in ALT cells, although the influence of G4 stabilization on the ALT mechanism has so far been poorly investigated. Here we show that sensitivity to RHPS4 is comparable in ALT-positive (U2OS; SAOS-2) and telomerase-positive (HOS) osteosarcoma cell lines, unlinking the telomere maintenance mechanism and RHPS4 responsiveness. To investigate the impact of G4 stabilization on ALT, the cardinal ALT hallmarks were analyzed. A significant induction of telomeric doublets, telomeric clusterized DNA damage, ALT-associated Promyelocytic Leukaemia-bodies (APBs), telomere sister chromatid exchanges (T-SCE) and c-circles was found exclusively in RHPS4-treated ALT cells. We surmise that RHPS4 affects ALT mechanisms through the induction of replicative stress that in turn is converted in DNA damage at telomeres, fueling recombination. In conclusion, our work indicates that RHPS4-induced telomeric DNA damage promotes overactivation of telomeric recombination in ALT cells, opening new questions on the therapeutic employment of G4 ligands in the treatment of ALT positive tumors.
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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.