ArticleNeuro-oncology2023
Wnt signaling regulates MFSD2A-dependent drug delivery through endothelial transcytosis in glioma.
Article in Neuro-oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 42 citations in OpenAlex.
- Plasma lipidomic and metabolomic profiles in high-grade glioma patients before and after 72-h presurgery water-only fasting.Molecular oncology · 2025Trial
- Role of the WNT signalling pathway in physiological and pathological blood-brain barrier.Annals of medicine · 2026Review
- MFSD2A in health and disease: lysolipid transport, barrier physiology, and translational boundaries.Molecular biomedicine · 2026Review
- Cell-to-Cell Signaling Networks at the Blood-Brain Barrier in Health and Disease.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Systems biology of Wnt signaling in glioma chemotherapy resistance: Integrating multi-omics mechanisms and emerging therapeutic vulnerabilities (Review).Oncology letters · 2026Review
- The regulatory network of Mfsd2a in cerebral ischemia: a novel time-targeted intervention framework.Molecular biology reports · 2026Review
- Humanized Murine Glioblastoma Models for Evaluation of Coxsackievirus Oncolytic Therapy.Cancers · 2026Article
- Targeting WTAP/ROR1/WNT5A-Mediated Crosstalk Between Glioma Stem Cells and Macrophages to Normalize Tumor Vasculature and Enhance Chemotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Overcoming tumor microenvironment barriers: transformable and bioinspired nanomedicine strategies for deep tumor penetration.Journal of nanobiotechnology · 2026Review
- LPC-engineered liposomes activate transcytosis for paclitaxel brain delivery and potentiation of TTFields/TMZ via TALECT regimen in glioblastoma.Theranostics · 2026Article
- MFSD2A: a molecular nexus linking blood-brain barrier, lipid metabolism, and ischemia-reperfusion injury.Cellular & molecular biology letters · 2025Review
- IRX3-CDK14 axis promotes glioblastoma progression by regulating LRP6-mediated canonical Wnt/β-catenin pathway.Cell death & disease · 2025Article
- RGS20 reduces glioma stemness and temozolomide resistance by intrinsically inhibiting the WNT/β-catenin signaling pathway.Scientific reports · 2025Article
- Keeping Wnt in check for efficient checkpoint blockade in glioblastoma.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Dual role of WNT10A in promoting the malignancy of glioblastoma and remodeling the tumor microenvironment.Neuro-oncology · 2025Article
- Effects of senescence on astrocyte to brain endothelial cell signaling.Neuroprotection (Chichester, England) · 2025Article
- GLUT3 enhances chemosensitivity in glioblastoma by transporting temozolomide and capecitabine.Cell death discovery · 2025Article
- The blood-brain barrier: a help and a hindrance.Brain : a journal of neurology · 2025Review
- Organelle-oriented nanomedicines in tumor therapy: Targeting, escaping, or collaborating?Bioactive materials · 2025Review
- Wnt/β-catenin mediated signaling pathways in cancer: recent advances, and applications in cancer therapy.Molecular cancer · 2025Review
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSystemic delivery of anti-tumor therapeutic agents to brain tumors is thwarted by the blood-brain barrier (BBB), an organotypic specialization of brain endothelial cells (ECs). A failure of pharmacological compounds to cross BBB is one culprit for the dismal prognosis of glioblastoma (GBM) patients. Identification of novel vascular targets to overcome the challenges posed by the BBB in tumors for GBM treatment is urgently needed.
methodsTemozolomide (TMZ) delivery was investigated in CT2A and PDGFB-driven RCAS/tv-a orthotopic glioma models. Transcriptome analysis was performed on ECs from murine gliomas. Mfsd2a deficient, Cav1 deficient, and Mfsd2a EC-specific inducible mice were developed to study the underlying molecular mechanisms.
resultsWe demonstrated that inhibiting Wnt signaling by LGK974 could increase TMZ delivery and sensitize glioma to chemotherapy in both murine glioma models. Transcriptome analysis of ECs from murine gliomas revealed that Wnt signaling inhibition enhanced vascular transcytosis as indicated by the upregulation of PLVAP and downregulation of MFSD2A. Mfsd2a deficiency in mice enhances TMZ delivery in tumors, whereas constitutive expression of Mfsd2a in ECs suppresses the enhanced TMZ delivery induced by Wnt pathway inhibition in murine glioma. In addition, Wnt signaling inhibition enhanced caveolin-1 (Cav1)-positive caveolae-mediated transcytosis in tumor ECs. Moreover, Wnt signaling inhibitor or Mfsd2a deficiency fails to enhance TMZ penetration in tumors from Cav1-deficient mice.
conclusionsThese results demonstrated that Wnt signaling regulates MFSD2A-dependent TMZ delivery through a caveolae-mediated EC transcytosis pathway. Our findings identify Wnt signaling as a promising therapeutic target to improve drug delivery for GBM treatment.
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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.