| First Author | Waters SB | Year | 2022 |
| Journal | Life Sci Alliance | Volume | 5 |
| Issue | 1 | PubMed ID | 34670814 |
| Mgi Jnum | J:312925 | Mgi Id | MGI:6792249 |
| Doi | 10.26508/lsa.202101170 | Citation | Waters SB, et al. (2022) KIF13B-mediated VEGFR2 trafficking is essential for vascular leakage and metastasis in vivo. Life Sci Alliance 5(1) |
| abstractText | 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. |
