ArticlePloS one2011
Phosphorylation of Akt and ERK1/2 is required for VEGF-A/VEGFR2-induced proliferation and migration of lymphatic endothelium.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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.
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Who cites it
56 citing papers in PubMed, 96 citations in OpenAlex.
- Coronary Microvascular Dysfunction: Epidemiology, Pathophysiology, Diagnosis, and Treatment.MedComm · 2026Review
- Critical role of endothelial regulator of G protein signaling 5 in postnatal angiogenesis.Angiogenesis · 2026Article
- Endothelial VEGFR2 insufficiency promotes the transition of lymphatic to hematopoietic transcriptional programs.Angiogenesis · 2026Article
- Antibodies blocking PlGF or VEGF interactions with the NRP1 receptor mediate antiproliferative effects.The Journal of biological chemistry · 2026Article
- VEGFR2 is required for VEGF-C-VEGFR3-PI3Kα-mediated sprouting lymphangiogenesis.Nature communications · 2026Article
- Unraveling the impact of cancer-associated fibroblasts on lymphatic metastasis of head and neck squamous cell carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Antibodies blocking PlGF or VEGF interactions with the NRP1 receptor mediate anti-proliferative effects.bioRxiv : the preprint server for biology · 2025Article
- DHHC5 regulates lacteal function and intestinal lipid absorption by maintaining VEGFR2 localization in lipid rafts.Life metabolism · 2025Article
- Angiogenic and Immunomodulatory effects of embryonic stem cell derived mesenchymal stem cells in a murine model of ischemic hindlimb.Scientific reports · 2025Article
- PRL3-zumab as an anti-angiogenic therapy in neovascular eye diseases.Nature communications · 2025Article
- Lymphatic transport in anti-tumor immunity and metastasis.The Journal of experimental medicine · 2025Review
- Adropin exerts neuroprotection in an experimental rat model of Parkinson's disease.Iranian journal of basic medical sciences · 2025Article
- VEGFR2 blockade inhibits glioblastoma cell proliferation by enhancing mitochondrial biogenesis.Journal of translational medicine · 2024Article
- Single-cell RNA sequencing reveals cellular and molecular landscape of fetal cystic hygroma.BMC medical genomics · 2024Article
- Unraveling the Molecular Mechanisms of Activated Protein C (APC) in Mitigating Reperfusion Injury and Cardiac Ischemia: a Promising Avenue for Novel Therapeutic Interventions.Journal of cardiovascular translational research · 2024Review
- Human vascular organoids with a mosaicbioRxiv : the preprint server for biology · 2024Article
- NRP1 interacts with endoglin and VEGFR2 to modulate VEGF signaling and endothelial cell sprouting.Communications biology · 2024Article
- A 3D Human Lymphatic Vessel-on-Chip Reveals the Roles of Interstitial Flow and VEGF-A/C for Lymphatic Sprouting and Discontinuous Junction Formation.Cellular and molecular bioengineering · 2023Article
- Vascular Endothelial Growth Factor Receptor 2: Molecular Mechanism and Therapeutic Potential in Preeclampsia Comorbidity with Human Immunodeficiency Virus and Severe Acute Respiratory Syndrome Coronavirus 2 Infections.International journal of molecular sciences · 2022Review
- Integrin-specific hydrogels for growth factor-free vasculogenesis.NPJ Regenerative medicine · 2022Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
There is growing evidence that vascular endothelial growth factor-A (VEGF-A), a ligand of the receptor tyrosine kinases VEGFR1 and VEGFR2, promotes lymphangiogenesis. However, the underlying mechanisms by which VEGF-A induces the growth of lymphatic vessels remain poorly defined. Here we report that VEGFR2, not VEGFR1, is the primary receptor regulating VEGF-A-induced lymphangiogenesis. We show that specific inhibition of VEGF-A/VEGFR2 signaling with the fully human monoclonal antibody r84 significantly inhibits lymphangiogenesis in MDA-MB-231 tumors. In vitro experiments with primary human dermal lymphatic endothelial cells (LECs) demonstrate that blocking VEGF-A activation of VEGFR2, not VEGFR1, significantly inhibits VEGF-A-induced proliferation and migration of LECs. We show that VEGF-A stimulation of LECs leads to the phosphorylation of VEGFR2 (Tyr 951, 1054, 1059, 1175, and 1214) which subsequently triggers PKC dependent phosphorylation of ERK1/2 and PI3-K dependent phosphorylation of Akt. Additionally, we demonstrate that inhibitors that suppress the phosphorylation of ERK1/2 and Akt significantly block VEGF-A- induced proliferation and migration of LECs. Together, these results shed light on the mechanisms regulating VEGF-A-induced proliferation and migration of LECs, reveal that VEGFR2 is the primary signaling VEGF-A receptor on lymphatic endothelium, and suggest that therapeutic agents targeting the VEGF-A/VEGFR2 axis could be useful in blocking the pathological formation of lymphatic vessels.
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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.