ArticleJCI insight2023
Nucleolin promotes angiogenesis and endothelial metabolism along the oncofetal axis in the human brain vasculature.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- AS1411-Induced Lipidomic Alterations and Therapeutic Insights in U-87 Glioblastoma Cells.Biomolecules · 2026Article
- Role of SCF/c-KIT axis in pericyte TNT-guided vessel branching.Fluids and barriers of the CNS · 2026Article
- Extracellular Vesicle-Mediated Nucleolin Transfer in Glioblastoma: A Targetable Axis Driving Blood-Tumour Barrier Formation.Journal of extracellular vesicles · 2026Article
- Chronic cerebral hypoperfusion induces venous dysfunction via EPAS1 regulation in mice.Nature communications · 2025Article
- Donor Age Impairs Vasculogenic Potential of hiPSC-Derived Endothelial Progenitors.bioRxiv : the preprint server for biology · 2025Article
- The MYC/TXNIP axis mediates NCL-Suppressed CD8Molecular medicine (Cambridge, Mass.) · 2025Article
- Single-cell atlas of the human brain vasculature across development, adulthood and disease.Nature · 2024Article
- Article
- Sex-Dependent Manifestations of Intracranial Aneurysms.Stroke (Hoboken, N.J.) · 2024Article
- Identification of a T2-hyperintense Perivascular Space in Brain Arteriovenous Malformations.In vivo (Athens, Greece)Article
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Authors and funding
20 authors at 13 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glioblastomas are among the deadliest human cancers and are highly vascularized. Angiogenesis is dynamic during brain development, almost quiescent in the adult brain but reactivated in vascular-dependent CNS pathologies, including brain tumors. The oncofetal axis describes the reactivation of fetal programs in tumors, but its relevance in endothelial and perivascular cells of the human brain vasculature in glial brain tumors is unexplored. Nucleolin is a regulator of cell proliferation and angiogenesis, but its roles in the brain vasculature remain unknown. Here, we studied the expression of Nucleolin in the neurovascular unit in human fetal brains, adult brains, and human gliomas in vivo as well as its effects on sprouting angiogenesis and endothelial metabolism in vitro. Nucleolin is highly expressed in endothelial and perivascular cells during brain development, downregulated in the adult brain, and upregulated in glioma. Moreover, Nucleolin expression correlated with glioma malignancy in vivo. In culture, siRNA-mediated Nucleolin knockdown reduced human brain endothelial cell (HCMEC) and HUVEC sprouting angiogenesis, proliferation, filopodia extension, and glucose metabolism. Furthermore, inhibition of Nucleolin with the aptamer AS1411 decreased brain endothelial cell proliferation in vitro. Mechanistically, Nucleolin knockdown in HCMECs and HUVECs uncovered regulation of angiogenesis involving VEGFR2 and of endothelial glycolysis. These findings identify Nucleolin as a neurodevelopmental factor reactivated in glioma that promotes sprouting angiogenesis and endothelial metabolism, characterizing Nucleolin as an oncofetal protein. Our findings have potential implications in the therapeutic targeting of glioma.
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