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KIF13B-mediated VEGFR2 trafficking is essential for vascular leakage and metastasis in vivo
journal contributionposted on 15.11.2022, 23:11 authored by Stephen B Waters, Joseph R Dominguez, Hyun-Dong Cho, Nicolene A Sarich, Asrar MalikAsrar Malik, Kaori YamadaKaori Yamada
VEGF-A induces vascular leakage and angiogenesis via activating the cell surface localized receptor VEGF receptor 2 (VEGFR2). The amount of available VEGFR2 at the cell surface is however tightly regulated by trafficking of VEGFR2 by kinesin family 13 B (KIF13B), a plus-end kinesin motor, to the plasma membrane of endothelial cells (ECs). Competitive inhibition of interaction between VEGFR2 and KIF13B by a peptide kinesin-derived angiogenesis inhibitor (KAI) prevented pathological angiogenesis in models of cancer and eye disease associated with defective angiogenesis. Here, we show the protective effects of KAI in VEGF-A-induced vascular leakage and cancer metastasis. Using an EC-specific KIF13B knockout (Kif13b iECKO ) mouse model, we demonstrated the function of EC expressed KIF13B in mediating VEGF-A-induced vascular leakage, angiogenesis, tumor growth, and cancer metastasis. Thus, KIF13B-mediated trafficking of VEGFR2 to the endothelial surface has an essential role in pathological angiogenesis induced by VEGF-A, and is therefore a potential therapeutic target.
Regulation of Angiogenesis through VEGFR2 Trafficking | Funder: National Institutes of Health (National Heart, Lung, and Blood Institute) | Grant ID: R56HL128342
Role of VEGFR2 trafficking in pathological angiogenesis in age related macular degeneration | Funder: National Institutes of Health (National Eye Institute) | Grant ID: R01EY029339
CitationWaters, S. B., Dominguez, J. R., Cho, H. -D., Sarich, N. A., Malik, A. B.Yamada, K. H. (2021). KIF13B-mediated VEGFR2 trafficking is essential for vascular leakage and metastasis in vivo. Life Science Alliance, 5(1), e202101170-. https://doi.org/10.26508/lsa.202101170
PublisherLife Science Alliance, LLC
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Cancer2.1 Biological and endogenous factors1.1 Normal biological development and functioningCardiovascularAnimalsCapillary PermeabilityCell MembraneDisease Models, AnimalEndothelial CellsKinesinsMembrane ProteinsMiceMice, KnockoutNeoplasm MetastasisNeoplasmsNeovascularization, PathologicProtein TransportVascular Endothelial Growth Factor Receptor-2