Gas6/Axl pathway promotes tumor invasion through the transcriptional activation of slug in hepatocellular carcinoma
Journal
Carcinogenesis
Journal Volume
35
Journal Issue
4
Pages
769-775
Date Issued
2014
Author(s)
Abstract
Hepatocellular carcinoma (HCC) is one of the most common fatal cancers worldwide. Other than the sorafenib treatment, no effective systemic therapy has been available thus far. Most targets in molecularly targeted therapy for cancer are receptor tyrosine kinases (RTKs). Therefore, identifying activated RTKs in HCC is critical for developing new molecularly targeted therapies. Using a phospho-RTK array, we found that Axl is one of the most frequently activated RTKs in liver cancer cell lines. The knockdown of Axl by RNA interference significantly reduced cell migration and invasion in the HCC cell lines HA22T and Mahlavu. Stimulation of HCC cell lines by Axl ligand growth arrest-specific 6 (Gas6) enhanced cell migration and invasion. The Gas6/Axl pathway enhanced the expression of the epithelial-mesenchymal transition-inducing transcription factor Slug, which is essential for the invasion-promoting activity of Axl. Treating HCC cells with the Axl inhibitor bosutinib suppressed Slug expression and decreased the invasiveness of HCC cell lines. These findings indicate that Gas6/Axl regulates tumor invasion through the transcriptional activation of Slug. ? The Author 2013. Published by Oxford University Press. All rights reserved.
SDGs
Other Subjects
Axl protein; bosutinib; growth arrest specific protein 6; protein tyrosine kinase; transcription factor Slug; unclassified drug; article; cancer cell; cell invasion; cell migration; clinical article; epithelial mesenchymal transition; gene silencing; human; human cell; human cell culture; liver cell carcinoma; molecularly targeted therapy; priority journal; protein expression; RNA interference; transcription initiation; tumor invasion; Carcinoma, Hepatocellular; Cell Line, Tumor; DNA Primers; Gene Knockdown Techniques; Humans; Intercellular Signaling Peptides and Proteins; Liver Neoplasms; Neoplasm Invasiveness; Real-Time Polymerase Chain Reaction; RNA Interference; Transcription Factors; Transcriptional Activation
Publisher
Oxford University Press
Type
journal article