ArticleJournal of experimental & clinical cancer research : CR2021
Downregulated CLIP3 induces radioresistance by enhancing stemness and glycolytic flux in glioblastoma.
Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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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
26 citing papers in PubMed, 41 citations in OpenAlex.
- Uncovering hypothesis-generating associations between prescription drugs and digestive cancer risk: a case-control drug-wide association study (DWAS).Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026Article
- Targeting the KAT7/H3K14ac/RAC2 Axis Mediates OXPHOS to Promote Stemness Maintenance and Malignancy in Glioblastoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Adenylate kinase 4 promotes radioresistance by suppressing radiation-induced ferroptosis through metabolic regulation in glioblastoma.Apoptosis : an international journal on programmed cell death · 2026Article
- Lipid metabolism in cancer stem cells: reprogramming, mechanisms, crosstalk, and therapeutic approaches.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Glucose and antidiabetic therapy in temozolomide resistance in glioblastoma.World journal of clinical oncology · 2025Review
- Scalable and unsupervised discovery from raw sequencing reads using SPLASH2.Nature biotechnology · 2025Article
- Combining Sulfonylureas with Anticancer Drugs: Evidence of Synergistic Efficacy with Doxorubicin In Vitro and In Vivo.International journal of molecular sciences · 2025Article
- Integrating multiomics analysis and machine learning to refine the molecular subtyping and prognostic analysis of stomach adenocarcinoma.Scientific reports · 2025Article
- Quercetin through miR-147-5p/Clip3 axis reducing Th17 cell differentiation to alleviate periodontitis.Regenerative therapy · 2024Article
- PIWIL2/PDK1 Axis Promotes the Progression of Cervical Epithelial Lesions via Metabolic Reprogramming to Maintain Tumor-Initiating Cell Stemness.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Transcription factors ASCL1 and OLIG2 drive glioblastoma initiation and co-regulate tumor cell types and migration.Nature communications · 2024Article
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Shedding light on function of long non-coding RNAs (lncRNAs) in glioblastoma.Non-coding RNA research · 2024Review
- Hypoxic microenvironment-induced exosomes confer temozolomide resistance in glioma through transfer of pyruvate kinase M2.Discover oncology · 2024Article
- SPLASH2 provides ultra-efficient, scalable, and unsupervised discovery on raw sequencing reads.bioRxiv : the preprint server for biology · 2024Article
- Puberty classifications in beef heifers are moderately to highly heritable and associated with candidate genes related to cyclicity and timing of puberty.Frontiers in genetics · 2024Article
- Myriad factors and pathways influencing tumor radiotherapy resistance.Open life sciences · 2024Review
- Progress in Glioma Stem Cell Research.Cancers · 2023Review
- Crosstalk between Noncoding RNAs and the Epigenetics Machinery in Pediatric Tumors and Their Microenvironment.Cancers · 2023Review
- DGKB mediates radioresistance by regulating DGAT1-dependent lipotoxicity in glioblastoma.Cell reports. Medicine · 2023Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGlioblastoma Multiforme (GBM) is a malignant primary brain tumor in which the standard treatment, ionizing radiation (IR), achieves a median survival of about 15 months. GBM harbors glioblastoma stem-like cells (GSCs), which play a crucial role in therapeutic resistance and recurrence.
methodsPatient-derived GSCs, GBM cell lines, intracranial GBM xenografts, and GBM sections were used to measure mRNA and protein expression and determine the related molecular mechanisms by qRT-PCR, immunoblot, immunoprecipitation, immunofluorescence, OCR, ECAR, live-cell imaging, and immunohistochemistry. Orthotopic GBM xenograft models were applied to investigate tumor inhibitory effects of glimepiride combined with radiotherapy.
resultsWe report that GSCs that survive standard treatment radiation upregulate Speedy/RINGO cell cycle regulator family member A (Spy1) and downregulate CAP-Gly domain containing linker protein 3 (CLIP3, also known as CLIPR-59). We discovered that Spy1 activation and CLIP3 inhibition coordinately shift GBM cell glucose metabolism to favor glycolysis via two cellular processes: transcriptional regulation of CLIP3 and facilitating Glucose transporter 3 (GLUT3) trafficking to cellular membranes in GBM cells. Importantly, in combination with IR, glimepiride, an FDA-approved medication used to treat type 2 diabetes mellitus, disrupts GSCs maintenance and suppresses glycolytic activity by restoring CLIP3 function. In addition, combining radiotherapy and glimepiride significantly reduced GBM growth and improved survival in a GBM orthotopic xenograft mouse model.
conclusionsOur data suggest that radioresistant GBM cells exhibit enhanced stemness and glycolytic activity mediated by the Spy1-CLIP3 axis. Thus, glimepiride could be an attractive strategy for overcoming radioresistance and recurrence by rescuing CLIP3 expression.
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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.