FAK inhibition decreases hepatoblastoma survival both in vitro and in vivo

Lauren A. Gillory, Jerry E. Stewart, Michael L. Megison, Hugh C. Nabers, Elizabeth Mroczek-Musulman, Elizabeth A. Beierle

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)206-215
Number of pages10
JournalTranslational Oncology
Volume6
Issue number2
DOIs
StatePublished - Apr 2013
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'FAK inhibition decreases hepatoblastoma survival both in vitro and in vivo'. Together they form a unique fingerprint.

Cite this