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dc.contributor.authorYu, Jinlongen_US
dc.contributor.authorZhang, Xuefengen_US
dc.contributor.authorKuzontkoski, Paula Men_US
dc.contributor.authorJiang, Shuxianen_US
dc.contributor.authorZhu, Weiquanen_US
dc.contributor.authorLi, Dean Yen_US
dc.contributor.authorGroopman, Jerome Een_US
dc.date.accessioned2014-09-08T15:37:46Z
dc.date.issued2014en_US
dc.identifier.citationYu, Jinlong, Xuefeng Zhang, Paula M Kuzontkoski, Shuxian Jiang, Weiquan Zhu, Dean Y Li, and Jerome E Groopman. 2014. “Slit2N and Robo4 regulate lymphangiogenesis through the VEGF-C/VEGFR-3 pathway.” Cell Communication and Signaling : CCS 12 (1): 25. doi:10.1186/1478-811X-12-25. http://dx.doi.org/10.1186/1478-811X-12-25.en
dc.identifier.issn1478-811Xen
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:12785974
dc.description.abstractBackground: Signaling 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. Results: We 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. Conclusion: These 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.en
dc.language.isoen_USen
dc.publisherBioMed Centralen
dc.relation.isversionofdoi:10.1186/1478-811X-12-25en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4122147/pdf/en
dash.licenseLAAen_US
dc.subjectSlit2en
dc.subjectRobo4en
dc.subjectVEGF-Cen
dc.subjectVEGFR-3en
dc.subjectAkten
dc.subjectPI3Ken
dc.subjectProliferationen
dc.subjectMigrationen
dc.subjectLymphangiogenesisen
dc.titleSlit2N and Robo4 regulate lymphangiogenesis through the VEGF-C/VEGFR-3 pathwayen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalCell Communication and Signaling : CCSen
dash.depositing.authorYu, Jinlongen_US
dc.date.available2014-09-08T15:37:46Z
dc.identifier.doi10.1186/1478-811X-12-25*
dash.contributor.affiliatedZhang, Xuefeng
dash.contributor.affiliatedGroopman, Jerome
dash.contributor.affiliatedKuzontkoski, Paula Marie
dash.contributor.affiliatedYu, Jinlong
dash.contributor.affiliatedJiang, Shuxian


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