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KIF13B - mediated VEGFR2 trafficking is essential for vascular leakage and metastasis in vivo

journal contribution
posted on 15.11.2022, 23:47 authored by Stephen B Waters, Joseph R Dominguez, Hyun-Dong Cho, Nicolene A Sarich, Asrar B 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 (Kif13biECKO) 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. 

Funding

National Institutes of Health (NIH) | 1R01EY029339-01A1 | KH Yamada

National Institutes of Health (NIH) | 1R56HL128342-01A1 | KH Yamada

RPB Stein Innovation Award | AB Malik

UIC Chancellor’s Innovation Fund | KH Yamada

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Citation

Waters, 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). https://doi.org/10.26508/Isa.202101170

Publisher

Life Science Alliance

Language

en

issn

2575-1077

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