ArticleProceedings of the National Academy of Sciences of the United States of America2025
A zinc transporter drives glioblastoma progression via extracellular vesicles-reprogrammed microglial plasticity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 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.
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Who cites it
11 citing papers in PubMed.
- Transcriptomic Evidence Identifies Two TMBIM Subgroups with Opposing Prognostic Associations in Glioma.Biology · 2026Article
- Extracellular vesicles in solid tumors: from tumor ecology to engineered therapeutics.Molecular cancer · 2026Review
- Zinc-induced exposure of an LxL motif drives clathrin-mediated endocytosis of the zinc transceptor ZIP4.The Journal of biological chemistry · 2026Article
- Review
- NIBAN2/FLII/RREB1 Axis Drives Glioma Stem Cell Malignancy via TLR3 Pathway Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Glioblastoma exosomes reprogramming the tumor microenvironment and evading therapeutic challenges.Molecular biology reports · 2026Review
- Metal Ions Within the Neuro-Immune-Tumor Axis.Journal of immunology research · 2026Review
- Extracellular vesicles as nanocarriers in glioblastoma: implications for chemoresistance and immune evasion.Frontiers in molecular neuroscience · 2026Review
- Evaluation of Ferroptosis as a Biomarker to Predict Treatment Outcomes of Cancer Immunotherapy.Cancer research communications · 2025Article
- Resveratrol suppresses OSCC invasion and migration by regulating macrophage polarization via Syk signaling pathway.Frontiers in immunology · 2025Article
- SLC30 (ZnT) and SLC39 (ZIP) zinc transporter families: from gatekeepers of zinc homeostasis to promoters of tumorigenesis and targets for clinical therapy.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
19 authors.
Funding
Abstract
Glioblastoma (GBM) is the most aggressive form of brain cancer, with limited therapeutic options. While microglia contribute to GBM progression, the mechanisms by which they foster a protumorigenic immune environment remain poorly understood. We identify the zinc transporter Zrt- And Irt-Like Protein 4 (ZIP4) as a pivotal regulator of the GBM immune landscape. In orthotopic mouse models, ZIP4 drives tumor growth and behavioral changes. Mechanistically, ZIP4 modulates microglial plasticity through tumor-derived extracellular vesicles carrying triggering receptor expressed on myeloid cells-1 (TREM1), a process regulated by the zinc-dependent transcription factor Zinc Finger E-box Binding Homeobox 1 in GBM cells. TREM1 enhances microglial plasticity through the spleen associated tyrosine kinase-Pyruvate dehydrogenase kinase-signal transducer and activator of transcription 3 (SYK-PDK-STAT3) signaling axis, ultimately promoting an immune environment favorable to tumor progression. ZIP4 depletion or TREM1 inhibition attenuates tumor growth and behavioral effects in vivo by disrupting the tumor-microglia interaction. These findings establish ZIP4 as a key modulator of the GBM immune landscape and suggest a promising therapeutic target to counteract microglia-mediated tumor progression.
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