Novel Mechanism Involved In The Regulation Ofoncogenic Axl Receptor Tyrosine Kinase In Cancer

Background: Oncogenic receptor tyrosine kinase Axl is overexpressed and plays an important role in multiple human cancers. However the mechanisms of Axl overexpression in cancer remain unclear. This study is to investigate the mechanisms that regulate Axl expression in pancreatic cancer.Experimental procedures: The interactions between HPK1, Axl and c-Cbl were examined using co-immunoprecipitation and immunoblotting. Inhibitors of endocytic pathway and immunofluorescence were used to examine the underlying mechanisms of HPK1-mediated Axl degradation. The functional significance of HPK1-mediated Axl degradation in the invasive capability of pancreatic ductal adenocarcinoma (PDAC) cells and it downstream signaling pathways were examined using HPK1 stable PDAC cells. Immunohistochemistry was used to examine the in vivo correlation between HPK1 and Axl in human pancreatic …