Inhibition of the focal adhesion kinase and vascular endothelial growth factor receptor-3 interaction leads to decreased survival in human neuroblastoma cell lines
Article first published online: 12 OCT 2012
© 2013 Wiley Periodicals, Inc.
Volume 53, Issue 3, pages 230–242, March 2014
How to Cite
Beierle, E. A., Ma, X., Stewart, J. E., Megison, M., Cance, W. G. and Kurenova, E. V. (2014), Inhibition of the focal adhesion kinase and vascular endothelial growth factor receptor-3 interaction leads to decreased survival in human neuroblastoma cell lines. Mol. Carcinog., 53: 230–242. doi: 10.1002/mc.21969
- Issue published online: 21 FEB 2014
- Article first published online: 12 OCT 2012
- Manuscript Accepted: 14 SEP 2012
- Manuscript Revised: 11 SEP 2012
- Manuscript Received: 11 JUN 2012
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. © 2012 Wiley Periodicals, Inc.