AXL is a member of the receptor tyrosine kinase (RTK) family that spans from the cytoplasm into the extracellular matrix and transmits signals by binding growth factors and other molecules and is involved with cellular proliferation.  Due to this, AXL (specifically its over-expression) is a known player in several cancers, including but not limited to: leukemia, colon cancer, thyroid carcinomas and melanomas.  The gene coding for this receptor kinase is found proximal to the now-infamous BCL-3 oncogene.

In a recent study, researchers at the Department of Molecular Medicine and Biotechnology at the University of Naples and the Institute of Experimental Endocrinology and Oncology “G. Salvatore”, also in Naples, have elucidated a novel understanding of the dependence of AXL on the chaperone Hsp90 for stability, proper protein folding and membrane translocation.

Like many other oncogenes, it seems that the prominent chaperone Hsp90 is pivotal for survival and proliferation of AXL, as it has been shown for other receptor tyrosine kinases.  By using the Geldanamycin derivative, 17-AAG (an inhibitor of Hsp90), the researchers demonstrated that by rendering Hsp90 non-functional, AXL increasingly becomes degraded by the ubiquitin/proteosome pathway.  In the presence of 17-AAG, nascent AXL was found to be improperly folded and degraded; whereas mature AXL was found to be depleted by its lack of presence on the plasma membrane.  This was achieved by using HeLa and thyroid carcinoma cell lines and confirmed by immunofluorescence, immunoprecipitation, pulse-chase analysis and several other experimental methods.

They conclude that AXL is dependent on Hsp90 for proper functionality and stability and point to Hsp90 (yet again) as a possible target in order to treat cancers characterized by AXL over-expression.

The original research paper was published in: The Journal of Biological Chemistry (April 2013)

Molecular mechanism of 17-Allylamino-17-demethoxygeldanamycin (17-AAG) induced AXL degradation.

This study made use of antibodies for Hsp90 and Hsp70 as well as the Hsp90 inhibitor 17-AAG.  StressMarq has an extensive range of antibodies for Hsp90 and Hsp70.  We also offer 17-AAG (product# SIH-100A).