Inhibition of the focal adhesion kinase and vascular endothelial growth factor receptor-3 interaction leads to decreased survival in human neuroblastoma cell lines.
Neuroblastoma continues to be a devastating childhood solid tumor and is responsible for over 15% of all childhood cancer-related deaths. Focal adhesion kinase (FAK) and vascular endothelial growth factor receptor-3 (VEGFR-3) are protein tyrosine kinases that are overexpressed in a number of human cancers, including neuroblastoma. These two kinases can directly interact and provide survival signals to cancer cells. In this study, we utilized siRNA to VEGFR-3 to demonstrate the biologic importance of this kinase in neuroblastoma cell survival. We also used confocal microscopy and immunoprecipitation to show that FAK and VEGFR-3 bind in neuroblastoma. Finally, employing a 12-amino-acid peptide (AV3) specific to VEGFR-3, we showed that the colocalization between FAK and VEGFR-3 could be disrupted, and that disruption resulted in decreased neuroblastoma cell survival. These studies provide insight to the FAK-VEGFR-3 interaction in neuroblastoma and demonstrate its importance in this tumor type. Focusing upon the FAK-VEGFR-3 interaction may provide a novel therapeutic target for the development of new strategies for treatment of neuroblastoma.
University of Alabama, Birmingham, Birmingham, Alabama.
Elizabeth A
EA
Beierle
Xiaojie
X
Ma
Jerry E
JE
Stewart
Michael
M
Megison
William G
WG
Cance
Elena V
EV
Kurenova
D017209:Apoptosis; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D005455:Fluorescent Antibody Technique; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D054730:Protein Interaction Domains and Motifs; D034741:RNA, Small Interfering / Q000235:genetics; D014407:Tumor Cells, Cultured; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D034741:RNA, Small Interfering; D040321:Vascular Endothelial Growth Factor Receptor-3; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human