ArticleThe Journal of clinical investigation2016
c-Met-mediated endothelial plasticity drives aberrant vascularization and chemoresistance in glioblastoma.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
87 citing papers in PubMed, 3 syntheses or guidelines pooled it, 122 citations in OpenAlex.
- What is the Impact of Endothelial-to-Mesenchymal Transition in Solid Tumours: A Qualitative Systematic Review and Quantitative Meta-Analysis.International journal of biological sciences · 2025Pooled it
- Implication of Irisin in Different Types of Cancer: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2022Pooled it
- Overexpression of c-Met is Associated with Poor Prognosis in Glioblastoma Multiforme: A Systematic Review and Meta-Analyses.Asian Pacific journal of cancer prevention : APJCP · 2021Pooled it
- Trial
- Reframing cancer therapy through tumor plasticity.Nature cancer · 2026Review
- Tumor-Intrinsic HEXB Drives Endothelial-To-Mesenchymal Transition and Confers Resistance to Anti-Angiogenic Therapy in Glioblastoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Engineered Microvascular Model of the Blood-Brain-Tumor Barrier Reveals Endothelial Remodeling in Diffuse Midline Glioma.Advanced healthcare materials · 2026Article
- The Roles of Transcription Factor Ets-1 in Neurological Disorders.Molecular neurobiology · 2026Review
- Nerve growth factor receptor (NGFR): A key player in glioblastoma progression.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- Tumour endothelial cell reprogramming orchestrates angiocrine signalling to drive chemoresistance in breast cancer.Angiogenesis · 2026Article
- Microenvironmental regulation of solid tumour resistance to CAR T cell therapy.Nature reviews. Immunology · 2026Review
- APOA2-mediated endothelial mesenchymal transition and cancer lipid metabolism reprogramming confers antiangiogenic drug resistance through TGF-β.Cell death discovery · 2026Article
- Article
- Loss of Fibronectin Fiber Tension in Glioblastoma is Associated with Microvascular Proliferations and Immune Cell Infiltration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- Loss of primary cilia promotes EphA2-mediated endothelial-to-mesenchymal transition in the ovarian tumor microenvironment.Molecular oncology · 2025Article
- Endothelial transdifferentiation of glioma stem cells: a literature review.Acta neuropathologica communications · 2025Review
- Shifting Shapes: The Endothelial-to-Mesenchymal Transition as a Driver for Cancer Progression.International journal of molecular sciences · 2025Review
- Spatial transcriptomics and multi-omics reveal relapse and resistance mechanisms of EndMT-derived CAFs mediated by TNC and FLNC in glioblastoma.Journal of translational medicine · 2025Article
- Angiogenesis and targeted therapy in the tumour microenvironment: From basic to clinical practice.Clinical and translational medicine · 2025Review
27 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 2 institutions in 2 countries.
Funding
Abstract
Aberrant vascularization is a hallmark of cancer progression and treatment resistance. Here, we have shown that endothelial cell (EC) plasticity drives aberrant vascularization and chemoresistance in glioblastoma multiforme (GBM). By utilizing human patient specimens, as well as allograft and genetic murine GBM models, we revealed that a robust endothelial plasticity in GBM allows acquisition of fibroblast transformation (also known as endothelial mesenchymal transition [Endo-MT]), which is characterized by EC expression of fibroblast markers, and determined that a prominent population of GBM-associated fibroblast-like cells have EC origin. Tumor ECs acquired the mesenchymal gene signature without the loss of EC functions, leading to enhanced cell proliferation and migration, as well as vessel permeability. Furthermore, we identified a c-Met/ETS-1/matrix metalloproteinase-14 (MMP-14) axis that controls VE-cadherin degradation, Endo-MT, and vascular abnormality. Pharmacological c-Met inhibition induced vessel normalization in patient tumor-derived ECs. Finally, EC-specific KO of Met inhibited vascular transformation, normalized blood vessels, and reduced intratumoral hypoxia, culminating in suppressed tumor growth and prolonged survival in GBM-bearing mice after temozolomide treatment. Together, these findings illustrate a mechanism that controls aberrant tumor vascularization and suggest that targeting Endo-MT may offer selective and efficient strategies for antivascular and vessel normalization therapies in GBM, and possibly other malignant tumors.
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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.