Journal
LIFE SCIENCE ALLIANCE
Volume 5, Issue 1, Pages -Publisher
LIFE SCIENCE ALLIANCE LLC
DOI: 10.26508/Isa.202101170
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Funding
- National Institutes of Health (NIH) [1R01EY029339-01A1, 1R56HL128342-01A1]
- Research to Prevent Blindness (RPB) Stein Innovation Award
- UIC Chancellor's Innovation Fund
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Research demonstrates that KAI has protective effects in VEGF-A-induced vascular leakage and cancer metastasis, while an EC-specific KIF13B knockout mouse model reveals the role of KIF13B in regulating pathological angiogenesis, vascular leakage, tumor growth, and cancer metastasis induced by VEGF-A.
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.
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