ArticleJCI insight2018
Temporal DNA-PK activation drives genomic instability and therapy resistance in glioma stem cells.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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.
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.
Who cites it
43 citing papers in PubMed, 62 citations in OpenAlex.
- Molecular insights into DNA damage response plasticity in glioma stem cells.Communications biology · 2026Review
- DNA damage response profile distinguishes poor-acting gliomas with shared methylome signatures.Neuro-oncology · 2026Article
- Cisplatin-mediated activation of NF-κB promotes lung cancer stem cell formation via DNA repair pathways.Journal of translational medicine · 2025Article
- Article
- Stem cell therapies and glioma stem cells in glioblastoma: a systematic review of current challenges and research directions.International journal of emergency medicine · 2025Review
- Prognostic signature detects homologous recombination deficient in glioblastoma.Translational cancer research · 2024Article
- miRNAs in radiotherapy resistance of cancer; a comprehensive review.Cell biochemistry and biophysics · 2024Review
- ARF4-mediated retrograde trafficking as a driver of chemoresistance in glioblastoma.Neuro-oncology · 2024Article
- DNA damage response in brain tumors: A Society for Neuro-Oncology consensus review on mechanisms and translational efforts in neuro-oncology.Neuro-oncology · 2024Review
- BUB1 regulates non-homologous end joining pathway to mediate radioresistance in triple-negative breast cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- The cGAS-Ku80 complex regulates the balance between two end joining subpathways.Cell death and differentiation · 2024Article
- Targeting DNA Repair and Survival Signaling in Diffuse Intrinsic Pontine Gliomas to Prevent Tumor Recurrence.Molecular cancer therapeutics · 2024Article
- Decoding mitochondrial DNA damage and repair associated withFrontiers in cellular and infection microbiology · 2024Review
- The nuclear factor erythroid 2-related factor 2/p53 axis in breast cancer.Biochemia medica · 2023Review
- DNA‑PKcs phosphorylation specific inhibitor, NU7441, enhances the radiosensitivity of clinically relevant radioresistant oral squamous cell carcinoma cells.Biomedical reports · 2023Article
- Review
- DNA Damage Response in Cancer Therapy and Resistance: Challenges and Opportunities.International journal of molecular sciences · 2022Review
- EGFR suppresses p53 function by promoting p53 binding to DNA-PKcs: a noncanonical regulatory axis between EGFR and wild-type p53 in glioblastoma.Neuro-oncology · 2022Article
- Flap endonuclease 1 and DNA-PKcs synergistically participate in stabilizing replication fork to encounter replication stress in glioma cells.Journal of experimental & clinical cancer research : CR · 2022Article
- Perspective on the Use of DNA Repair Inhibitors as a Tool for Imaging and Radionuclide Therapy of Glioblastoma.Cancers · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Cancer stem cells (CSCs) - known to be resistant to genotoxic radiation and chemotherapy - are fundamental to therapy failure and cancer relapse. Here, we reveal that glioma CSCs are hypersensitive to radiation, but a temporal DNA repair mechanism converts the intrinsic sensitivity to genomic instability and treatment resistance. Transcriptome analysis identifies DNA-dependent protein kinase (DNA-PK) as a predominant DNA repair enzyme in CSCs. Notably, DNA-PK activity is suppressed after irradiation when ROS induce the dissociation of DNA-PKcs with Ku70/80, resulting in delayed DNA repair and radiosensitivity; subsequently, after ROS clearance, the accumulated DNA damage and robust activation of DNA-PK induce genomic instability, facilitated by Rad50-mediated cell-cycle arrest, leading to enhanced malignancy, CSC overgrowth, and radioresistance. Finally, we show a requisite in vivo role for DNA-PK in CSC-mediated radioresistance and glioma progression. These findings identify a time-sensitive mechanism controlling CSC resistance to DNA-damaging treatments and suggest DNA-PK/Rad50 as promising targets for CSC eradication.
Indexed as
Identifiers
What OpenQuestion holds
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.