RT Journal Article
SR Electronic
T1 KIF13B-mediated VEGFR2 trafficking is essential for vascular leakage and metastasis in vivo
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202101170
DO 10.26508/lsa.202101170
VO 5
IS 1
A1 Stephen B Waters
A1 Joseph R Dominguez
A1 Hyun-Dong Cho
A1 Nicolene A Sarich
A1 Asrar B Malik
A1 Kaori H Yamada
YR 2022
UL https://www.life-science-alliance.org/content/5/1/e202101170.abstract
AB 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.