ArticleNature communications2018
uPARAP/Endo180 receptor is a gatekeeper of VEGFR-2/VEGFR-3 heterodimerisation during pathological lymphangiogenesis.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Article
- AXL promotes lymphangiogenesis by amplifying VEGF-C-mediated AKT pathway.Cellular and molecular life sciences : CMLS · 2025Article
- Differential Expression of ARG1 and MRC2 in Retinal Müller Glial Cells During Autoimmune Uveitis.Biomolecules · 2025Article
- Regulation of VEGFR3 signaling in lymphatic endothelial cells.Frontiers in cell and developmental biology · 2025Review
- Lymphangiogenesis: novel strategies to promote cutaneous wound healing.Burns & trauma · 2024Review
- Downregulation of ITGA5 inhibits lymphangiogenesis and cell migration and invasion in male laryngeal squamous cell carcinoma.Protoplasma · 2023Article
- Current Status of Lymphangiogenesis: Molecular Mechanism, Immune Tolerance, and Application Prospect.Cancers · 2023Review
- Angiopoietin-2-induced lymphatic endothelial cell migration drives lymphangiogenesis via the β1 integrin-RhoA-formin axis.Angiogenesis · 2022Article
- Periostin in lymph node pre-metastatic niches governs lymphatic endothelial cell functions and metastatic colonization.Cellular and molecular life sciences : CMLS · 2022Article
- uPARAP/Endo180: a multifaceted protein of mesenchymal cells.Cellular and molecular life sciences : CMLS · 2022Review
- Review
- Prognostic and immunotherapeutic significance of mannose receptor C type II in 33 cancers: An integrated analysis.Frontiers in molecular biosciences · 2022Article
- Regulation of VEGFR Signalling in Lymphatic Vascular Development and Disease: An Update.International journal of molecular sciences · 2021Review
- Single-cell transcriptomic profiling and characterization of endothelial progenitor cells: new approach for finding novel markers.Stem cell research & therapy · 2021Article
- HEYL Regulates Neoangiogenesis Through Overexpression in Both Breast Tumor Epithelium and Endothelium.Frontiers in oncology · 2020Article
- Lymphatic Endothelial Cell Junctions: Molecular Regulation in Physiology and Diseases.Frontiers in physiology · 2020Review
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development of new lymphatic vessels occurs in many cancerous and inflammatory diseases through the binding of VEGF-C to its receptors, VEGFR-2 and VEGFR-3. The regulation of VEGFR-2/VEGFR-3 heterodimerisation and its downstream signaling in lymphatic endothelial cells (LECs) remain poorly understood. Here, we identify the endocytic receptor, uPARAP, as a partner of VEGFR-2 and VEGFR-3 that regulates their heterodimerisation. Genetic ablation of uPARAP leads to hyperbranched lymphatic vasculatures in pathological conditions without affecting concomitant angiogenesis. In vitro, uPARAP controls LEC migration in response to VEGF-C but not VEGF-A or VEGF-CCys156Ser. uPARAP restricts VEGFR-2/VEGFR-3 heterodimerisation and subsequent VEGFR-2-mediated phosphorylation and inactivation of Crk-II adaptor. uPARAP promotes VEGFR-3 signaling through the Crk-II/JNK/paxillin/Rac1 pathway. Pharmacological Rac1 inhibition in uPARAP knockout mice restores the wild-type phenotype. In summary, our study identifies a molecular regulator of lymphangiogenesis, and uncovers novel molecular features of VEGFR-2/VEGFR-3 crosstalk and downstream signaling during VEGF-C-driven LEC sprouting in pathological conditions.
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