Hepatoblastoma is the most frequently diagnosed liver
tumor of childhood, and children with advanced, metastatic or relapsed disease have a disease-free survival rate under 50%.
Focal adhesion kinase (FAK) is a nonreceptor
tyrosine kinase that is important in many facets of
tumor development and progression. FAK has been found in other pediatric solid
tumors and in adult
hepatocellular carcinoma, leading us to hypothesize that FAK would be present in
hepatoblastoma and would impact its cellular survival. In the current study, we showed that FAK was present and phosphorylated in human
hepatoblastoma tumor specimens. We also examined the effects of FAK inhibition upon
hepatoblastoma cells using a number of parallel approaches to block FAK including RNAi and small molecule FAK inhibitors. FAK inhibition resulted in decreased cellular survival, invasion, and migration and increased apoptosis. Further, small molecule inhibition of FAK led to decreased
tumor growth in a nude mouse xenograft model of
hepatoblastoma. The findings from this study will help to further our understanding of the regulation of
hepatoblastoma tumorigenesis and may provide desperately needed novel therapeutic strategies and targets for aggressive, recurrent, or metastatic
hepatoblastomas.