Focal Adhesion Kinase Mediates Gastrin-Releasing Peptide Receptor-Induced Neuroblastoma Progression
Lee, Sora
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2013-04-18
Abstract
Neuroblastomas express increased levels of gastrin-releasing peptide receptor (GRPR). However, the exact molecular mechanisms involved in GRPR-mediated cell signaling in neuroblastoma growth and metastasis are unknown. In this dissertation, I demonstrate that focal adhesion kinase (FAK), as a critical downstream target of GRPR, is an important regulator of neuroblastoma growth and metastasis. I modulated the expression of GRPR and FAK in cells and tested their functional role in tumor progression in vitro and in vivo. Additionally, I investigated the role of Integrins in regulation of FAK activation and cell migration in GRPR overexpressing neuroblastoma cells. Moreover, I evaluated the effect of a FAK inhibitor in vivo, which suppressed GRP-induced neuroblastoma growth and metastasis. Our results indicate that FAK is a critical downstream regulator of GRPR, which mediates tumorigenesis and metastasis in neuroblastoma.