ArticleThe Journal of clinical investigation2021
N-cadherin upregulation mediates adaptive radioresistance in glioblastoma.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.
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
74 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- LAK to CIK continuum in glioma immunotherapy: a systematic review of efficacy and safety outcomes.Journal of translational medicine · 2026Pooled it
- Therapy-induced IGF1R signaling as an actionable vulnerability in oncolytic virotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Construction Strategies, Microenvironmental Modelling and Precision-Therapy Applications of Glioma Organoid Models.Cancers · 2026Review
- Mechanisms, Microenvironments, and Models: Understanding Therapeutic Resistance in Glioblastoma.International journal of radiation oncology, biology, physics · 2026Review
- Article
- Exploring the immune environment of glioblastoma in humanized mouse models.Neuro-oncology · 2026Article
- Identification of a Novel Radiosensitivity-Related Signature and Validation of GPX8 in Regulating the Radiosensitivity of Glioma.CNS neuroscience & therapeutics · 2026Article
- Suppressive role of SCN4B in the epithelial‑mesenchymal transition of lung adenocarcinoma.Oncology reports · 2026Article
- NANP targeting radiosensitizes glioblastoma through TNFR1 sialylation-driven mesenchymal shift.Nature communications · 2026Article
- NK cell-derived GZMB (granzyme B) suppresses glioblastoma radioresistance by blocking SDC1-mediated autophagosome maturation.Autophagy · 2026Article
- Acute high-dose irradiation disrupts cell adhesion and Silk-Ovarioid formation in human primary ovarian cells.Journal of ovarian research · 2026Article
- Drug resistance in glioblastoma: Challenges, mechanisms and therapeutic strategies (Review).Molecular and clinical oncology · 2026Review
- No differences in therapeutic efficacy while sparing healthy tissue for orthotopic glioblastoma patient-derived xenografts in context of proton FLASH.Clinical and translational radiation oncology · 2026Article
- Druggable Mendelian randomization prioritizes CDH2 and supports finerenone as a candidate therapeutic strategy for diabetic retinopathy.Frontiers in pharmacology · 2026Article
- Overcoming IGF1R-Mediated Resistance to Oncolytic HSV1 and Radiotherapy via Triple Combination Therapy.Research square · 2025Article
- Pyrophosphate Regulates Multilineage Differentiation in Stem Cells From Human Exfoliated Deciduous Teeth.Clinical and experimental dental research · 2025Article
- Amlodipine exerts inhibitory effects against glioma stem cells through degrading EGFR and down-regulating its downstream pro-survival pathways.Cell death discovery · 2025Article
- A Novel Serum-Free Triculture Model of Glioblastoma, Astrocytes, and Macrophages.International journal of molecular sciences · 2025Article
- Glioblastoma shift from bulk to infiltrative growth is guided by plexin-B2-mediated microglia alignment in invasive niches.Nature cancer · 2025Article
- Xenoline-polarized macrophages as an alternative in vitro model of tumor-associated macrophages in glioblastoma.Acta neuropathologica communications · 2025Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Glioblastoma (GBM) is composed of heterogeneous tumor cell populations, including those with stem cell properties, termed glioma stem cells (GSCs). GSCs are innately less radiation sensitive than the tumor bulk and are believed to drive GBM formation and recurrence after repeated irradiation. However, it is unclear how GSCs adapt to escape the toxicity of repeated irradiation used in clinical practice. To identify important mediators of adaptive radioresistance in GBM, we generated radioresistant human and mouse GSCs by exposing them to repeat cycles of irradiation. Surviving subpopulations acquired strong radioresistance in vivo, which was accompanied by a reduction in cell proliferation and an increase in cell-cell adhesion and N-cadherin expression. Increasing N-cadherin expression rendered parental GSCs radioresistant, reduced their proliferation, and increased their stemness and intercellular adhesive properties. Conversely, radioresistant GSCs lost their acquired phenotypes upon CRISPR/Cas9-mediated knockout of N-cadherin. Mechanistically, elevated N-cadherin expression resulted in the accumulation of β-catenin at the cell surface, which suppressed Wnt/β-catenin proliferative signaling, reduced neural differentiation, and protected against apoptosis through Clusterin secretion. N-cadherin upregulation was induced by radiation-induced IGF1 secretion, and the radiation resistance phenotype could be reverted with picropodophyllin, a clinically applicable blood-brain-barrier permeable IGF1 receptor inhibitor, supporting clinical translation.
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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.