Yamada, K. H., Kang, H., Malik, A. B. Antiangiogenic Therapeutic Potential of Peptides Derived from the Molecular Motor KIF13B that Transports VEGFR2 to Plasmalemma in Endothelial Cells. Am J Pathol. 2017
Angiogenesis is a hallmark of cancer. The cancer cells need a blood supply to bring oxygen and nutrients to grow and survive. So they secrete VEGF to recruit new blood vessels in the tumor. So, inhibiting angiogenesis is a promising therapeutic approach for cancer. In fact, anti-VEGF drug Avastin was approved for many cancers including metastatic colorectal cancer, renal cell carcinoma, ovarian cancer, and glioblastoma.
VEGFR2 trafficking by KIF13B is required for angiogenesis. Then, can it be a therapeutic target?
KIF13B directly interacts with VEGFR2. So, what if we disrupt the interaction? Can we inhibit VEGFR2 trafficking to the cell surface? If VEGFR2 is not on the cell surface, it cannot receive VEGF stimuli, it cannot induce angiogenic signaling in the cells. Yes, that is actually true.
We defined minimum binding site within KIF13B for the interaction with VEGFR2, and synthesized as a small peptide, and named as KAI (Kinesin- derived Angiogenesis Inhibitor). KAI actually inhibited tumor angiogenesis and tumor growth in mouse model.
This figure is showing the immunohistochemistry of VEGFR2 and vWF, a marker for blood vessels, in tumor grown in mice. Treatment with KAI significantly inhibited tumor angiogenesis, compared to PBS (just saline).
Small peptide KAI inhibits cancer growth by inhibiting VEGFR2 trafficking and angiogenesis.
For the detail, please read the article.
Abbreviation
VEGF: vascular endothelial growth factor
VEGFR2: VEGF receptor 2
KIF13B: kinesin family 13B
KAI: kinesin-derived angiogenesis inhibitor