ArticleCell communication and signaling : CCS2014
Slit2N and Robo4 regulate lymphangiogenesis through the VEGF-C/VEGFR-3 pathway.
Article in Cell communication and signaling : CCS, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
- HIV-associated preeclampsia: evaluation of lymphangiogenesis in placental bed samples.Histochemistry and cell biology · 2025Article
- Regulation of VEGFR3 signaling in lymphatic endothelial cells.Frontiers in cell and developmental biology · 2025Review
- Emerging Role of the Slit/Roundabout (Robo) Signaling Pathway in Glioma Pathogenesis and Potential Therapeutic Options.Biomolecules · 2024Review
- Slit2-Robo4 signal pathway and tight junction in intestine mediate LPS-induced inflammation in mice.European journal of medical research · 2024Article
- Lymphangiogenesis Guidance Mechanisms and Therapeutic Implications in Pathological States of the Cornea.Cells · 2023Review
- RAF1 promotes lymphatic metastasis of hypopharyngeal carcinoma via regulating LAGE1: an experimental research.Journal of translational medicine · 2022Article
- The lymphatic vasculature: An active and dynamic player in cancer progression.Medicinal research reviews · 2022Review
- Fibroblast growth factor-2 alleviates the capillary leakage and inflammation in sepsis.Molecular medicine (Cambridge, Mass.) · 2020Article
- CD146, from a melanoma cell adhesion molecule to a signaling receptor.Signal transduction and targeted therapy · 2020Review
- Robo4 contributes to the turnover of Peyer's patch B cells.Mucosal immunology · 2020Article
- Rho-kinase inhibition by Fasudil promotes tumor maturation and apoptosis in small-cell lung cancer.American journal of translational research · 2020Article
- Angiogenesis, Lymphangiogenesis, and the Immune Response in South African Preeclamptic Women Receiving HAART.International journal of molecular sciences · 2019Review
- Inhibitory Effect of Slit2-N on VEGF165-induced proliferation of vascular endothelia via Slit2-N-Robo4-Akt pathway in choroidal neovascularization.Cell cycle (Georgetown, Tex.) · 2019Article
- Antagonistic effects of exogenous Slit2 on VEGF-induced choroidal endothelial cell migration and tube formation.Experimental and therapeutic medicine · 2019Article
- Lung Tumorigenesis Alters the Expression of Slit2-exon15 Splicing Variants in Tumor Microenvironment.Cancers · 2019Article
- The Role of the Slit/Robo Signaling Pathway.Journal of Cancer · 2019Review
- Robo 4 - the double-edged sword in prostate cancer: impact on cancer cell aggressiveness and tumor vasculature.International journal of medical sciences · 2019Article
- Modulation of VEGF-induced migration and network formation by lymphatic endothelial cells: Roles of platelets and podoplanin.Platelets · 2018Article
- Slit2 suppresses endothelial cell proliferation and migration by inhibiting the VEGF-Notch signaling pathway.Molecular medicine reports · 2017Article
- The lymphatic system and pancreatic cancer.Cancer letters · 2016Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundSignaling through vascular endothelial growth factor C (VEGF–C) and VEGF receptor 3 (VEGFR-3) plays a central role in lymphangiogenesis and the metastasis of several cancers via the lymphatics. Recently, the Slit2/Robo4 pathway has been recognized as a modulator of vascular permeability and integrity. Signaling via the Robo receptor inhibits VEGF-mediated effects; however, its effects on lymphatic endothelial cell function have not been well characterized.
resultsWe found that pretreatment with Slit2N, an active fragment of Slit2, inhibited VEGF-C-mediated lung-derived lymphatic endothelial cell (L-LEC) proliferation, migration, and in vitro tube formation. Slit2N induced the internalization of VEGFR-3, which blocked its activation, and inhibited the activation of the PI3K/Akt pathway by VEGF-C in L-LECs. Moreover, we found that inhibition of VEGF-C-induced effects by Slit2N was Robo4-dependent.
conclusionThese results indicate that Slit2N/Robo4 modulates several key cellular functions, which contribute to lymphangiogenesis, and identify this ligand-receptor pair as a potential therapeutic target to inhibit lymphatic metastasis of VEGF-C-overexpressing cancers and manage lymphatic dysfunctions characterized by VEGF-C/VEGFR-3 activation.
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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.