Integrated analysis of multiple receptor tyrosine kinases identifies Axl as a therapeutic target and mediator of resistance to sorafenib in hepatocellular carcinoma.

ABSTRACT:

Background

Aberrant activation of Axl is implicated in the progression of hepatocellular carcinoma (HCC). We explored the biologic significance and preclinical efficacy of Axl inhibition as a therapeutic strategy in sorafenib-naive and resistant HCC.

Methods

We evaluated Axl expression in sorafenib-naive and resistant (SR) clones of epithelial (HuH7) and mesenchymal origin (SKHep-1) using antibody arrays and confirmed tissue expression. We tested the effect of Axl inhibition with RNA-interference and pharmacologically with R428 on a number of phenotypic assays.

Results

Axl mRNA overexpression in cell lines (n = 28) and RNA-seq tissue datasets (n = 373) correlated with epithelial-to-mesenchymal transition (EMT). Axl was overexpressed in HCC compared to cirrhosis and no

SUBMITTER: Pinato DJ 

PROVIDER: S-EPMC6461770 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature