ArticleNeuro-oncology2025
Nuclear cholesterol regulates nuclear size and DNA damage responses in cancer stem cells.
Article in Neuro-oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
3 citing papers in PubMed.
- NAT10-dependent NCell reports · 2026Article
- Getting nuclear size just right - emerging mechanisms regulating nuclear scaling and morphology.Journal of cell science · 2026Review
- Molecular insights into DNA damage response plasticity in glioma stem cells.Communications biology · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
25 authors.
Funding
Abstract
backgroundNuclear atypia is associated with increased malignancy in numerous cancers, including glioblastoma (GBM). Here, we found that GBM stem cells display small nuclear size, prompting investigation of mechanisms underlying nuclear size regulation in the tumor hierarchy.
methodsWe performed comparative gene expression and proteomics in GBM stem cells (GSCs) and neural stem cells (NSCs) to discover potential regulators of nuclear size. Through transcriptomic analysis, mass spectrometry, and pharmacologic inhibition, we interrogated the functional significance of nuclear size regulation.
resultsGSCs were enriched for a nuclear sterol reductase, lamin B receptor (LBR). Targeting LBR increased nuclear size and decreased GSC viability and tumor initiation. Regulation of nuclear cholesterol synthesis underlaid LBR dependency in GSCs. Loss of LBR or reduction of cholesterol levels induced double-strand DNA breaks (DSBs), activating P53-dependent DNA damage response (DDR). The GSC proteomic LBR interactome revealed DDR mediators, including DEAD-box RNA helicase DDX5 that resolves R-loops at DSBs. Genetic targeting of LBR reduced the DDX5-R loop interaction, leading to increased R-loop formation rescued by cholesterol supplementation. Pharmacological sterol reductase inhibition mirrored genetic LBR targeting by reducing the DDX5-R loop interaction and increasing R-loops and DSBs. Targeting LBR genetically and pharmacologically inhibits GSC growth in vivo and synergizes with irradiation.
conclusionsStem-like GBM cells display reduced nuclear size, driven by nuclear cholesterol synthesis to regulate radiation responses, revealing a novel therapeutic paradigm.
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Registered trials
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