ArticleCell death & disease2019
R406 elicits anti-Warburg effect via Syk-dependent and -independent mechanisms to trigger apoptosis in glioma stem cells.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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Who cites it
31 citing papers in PubMed, 58 citations in OpenAlex.
- The perinecrotic niche of glioblastoma drives tumor-associated macrophage polarization and immunosuppression via podoplanin-mediated CLEC5A activation.The Journal of clinical investigation · 2026Article
- Systems biology-based drug repurposing for neuroinflammation treatment in activated human microglia.Scientific reports · 2026Article
- PIK-III-Mediated Elevation of Thiamine Re-Sensitises Renal Cell Carcinoma to Cuproptosis via Activating PDHA1.Cell proliferation · 2026Article
- Effective approaches in conquering chemoresistance of glioblastoma: potential for nanoformulations.Drug delivery and translational research · 2026Review
- Metabolic reprogramming and immunosenescence: a new sight for glioma therapy.Frontiers in cell and developmental biology · 2026Review
- Development of a comparative high-throughput screening platform for identifying glioblastoma subtype specific inhibitors.Cell insight · 2025Article
- Cancer stem cells: landscape, challenges and emerging therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- Article
- HDAC inhibitor MS275 reprograms metabolism to induce differentiation and suppress proliferation in hepatocellular carcinoma.Frontiers in immunology · 2025Article
- New insights into SYK targeting in solid tumors.Trends in pharmacological sciences · 2024Review
- Targeting DNM1L/DRP1-FIS1 axis inhibits high-grade glioma progression by impeding mitochondrial respiratory cristae remodeling.Journal of experimental & clinical cancer research : CR · 2024Article
- Hypoxia promotes metastasis by relieving miR-598-3p-restricted glycolysis in gastric cancer.Journal of translational medicine · 2024Article
- FLI1 induces erythroleukemia through opposing effects on UBASH3A and UBASH3B expression.BMC cancer · 2024Article
- Lipid metabolism dynamics in cancer stem cells: potential targets for cancers.Frontiers in pharmacology · 2024Review
- Role of Glycolytic and Glutamine Metabolism Reprogramming on the Proliferation, Invasion, and Apoptosis Resistance through Modulation of Signaling Pathways in Glioblastoma.International journal of molecular sciences · 2023Review
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- Article
- MicroRNA-339-5p inhibits lipopolysaccharide-induced rat mesangial cells by regulating the Syk/Ras/c-Fos pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2022Article
- Connexin32 regulates expansion of liver cancer stem cells via the PI3K/Akt signaling pathway.Oncology reports · 2022Article
- Targeting HDAC6 to Overcome Autophagy-Promoted Anti-Cancer Drug Resistance.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
19 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Given that glioma stem cells (GSCs) play a critical role in the initiation and chemoresistance in glioblastoma multiforme (GBM), targeting GSCs is an attractive strategy to treat GBM. Utilizing an anti-cancer compound library, we identified R406, the active metabolite of a FDA-approved Syk inhibitor for immune thrombocytopenia (ITP), with remarkable cytotoxicity against GSCs but not normal neural stem cells. R406 significantly inhibited neurosphere formation and triggered apoptosis in GSCs. R406 induced a metabolic shift from glycolysis to oxidative phosphorylation (OXPHOS) and subsequently production of excess ROS in GSCs. R406 also diminished tumor growth and efficiently sensitized gliomas to temozolomide in GSC-initiating xenograft mouse models. Mechanistically, the anti-GSC effect of R406 was due to the disruption of Syk/PI3K signaling in Syk-positive GSCs and PI3K/Akt pathway in Syk-negative GSCs respectively. Overall, these findings not only identify R406 as a promising GSC-targeting agent but also reveal the important role of Syk and PI3K pathways in the regulation of energy metabolism in GSCs.
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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.