Pharmacological inhibition of Axl tyrosine kinase as a novel therapeutic strategy in hepatocellular carcinoma.

e15152 Background: Aberrant activation of Axl tyrosine kinase and its ligand Gas-6 is implicated in the progression of hepatocellular carcinoma (HCC) by promoting cell survival, proliferation and motility. We explored the biological significance and preclinical efficacy of Axl inhibition as a therapeutic strategy in HCC. Methods: We confirmed Axl overexpression in a panel of immortalized HCC cell lines and in human tissue using immunohistochemistry. We tested pharmacological inhibition with Axl inhibitor R428 and RNA interference on cell cytotoxicity and apoptisis assays, cell cycle analysis, random motility assays, western blot (WB) and 18F-FDG uptake studies. Results: Axl mRNA overexpression was found in 13/28 cell lines and negatively correlated with E-cadherin expression (p = 0.001). In a restricted panel of 7 lines, WB confirmed Axl to correlate positively with Vimentin and negatively with E-cadherin expression, consistent with a mesenchymal phenotype. A significant overexpression gradient for Axl wa...