ArticleMolecular biology of the cell2006
Prox1 promotes lineage-specific expression of fibroblast growth factor (FGF) receptor-3 in lymphatic endothelium: a role for FGF signaling in lymphangiogenesis.
Article in Molecular biology of the cell, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 1 of them a synthesis that pooled it.
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100 citing papers in PubMed, 1 synthesis or guideline pooled it, 179 citations in OpenAlex.
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- Tissue engineering approaches for lymphedema: biomaterial innovations and clinical potential.Frontiers in cell and developmental biology · 2025Review
- Piezo1 regulates meningeal lymphatic vessel drainage and alleviates excessive CSF accumulation.Nature neuroscience · 2024Article
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- Molecular and metabolic orchestration of the lymphatic vasculature in physiology and pathology.Nature communications · 2023Review
- Lymph node metastasis in cancer progression: molecular mechanisms, clinical significance and therapeutic interventions.Signal transduction and targeted therapy · 2023Review
- The emerging roles of long noncoding RNAs in lymphatic vascular development and disease.Cellular and molecular life sciences : CMLS · 2023Review
- Isolation and short-term culturing of primary lymphatic endothelial cells from collecting lymphatics: A techniques study.Microcirculation (New York, N.Y. : 1994) · 2023Article
- Lymphangiogenesis Guidance Mechanisms and Therapeutic Implications in Pathological States of the Cornea.Cells · 2023Review
- Extracellular Vesicles Are Important Mediators That Regulate Tumor Lymph Node Metastasis via the Immune System.International journal of molecular sciences · 2023Review
- The natural FGF-trap long pentraxin 3 inhibits lymphangiogenesis and lymphatic dissemination.Experimental hematology & oncology · 2022Article
- The Role of PROX1 in Neoplasia: A Key Player Often Overlooked.Diagnostics (Basel, Switzerland) · 2022Review
- Lymphatic Tissue Bioengineering for the Treatment of Postsurgical Lymphedema.Bioengineering (Basel, Switzerland) · 2022Review
- The lymphatic vasculature: An active and dynamic player in cancer progression.Medicinal research reviews · 2022Review
- Vasohibin 2 promotes lymphangiogenesis of lung squamous cell carcinoma through snail-dependent vascular endothelial growth factor-D (VEGF-D) signaling pathway.Annals of translational medicine · 2022Article
40 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Fibroblast growth factors play important roles in angiogenesis, but their functions in lymphangiogenesis remain poorly understood. The homeodomain transcription factor Prox1 is essential for development of the lymphatic system by specifying lymphatic endothelial cell (LEC) fate. Here, we identify fibroblast growth factor (FGF) receptor (FGFR)-3 as a novel Prox1 target gene. Ectopic overexpression of Prox1 in blood vascular endothelial cells up-regulates FGFR-3. Prox1 induces the expression of the IIIc isoform, which we also found to be the major isoform of FGFR-3 expressed in LECs. This transcriptional activation is mediated by a direct binding of Prox1 to newly identified Prox1-response elements in the FGFR-3 promoter. Consistently, FGFR-3 is up-regulated in Prox1-positive newly formed lymphatic vessels during embryogenesis and its lymphatic-specific expression is maintained throughout development. We also found that FGF-1 and FGF-2 promote proliferation, migration, and survival of cultured LECs without involvement of vascular endothelial cell growth factor receptor-3. We show that FGF-2 binds to low- and high-affinity receptors on LECs and is efficiently internalized and processed. Moreover, functional inhibition of FGFR-3 using small interfering RNA represses LEC proliferation. Together, these results indicate that FGFR-3 is an initial target of Prox1 during the lymphatic cell fate specification and that FGF signaling may play an important role in lymphatic vessel development.
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