Cancer progression and non-genetic therapy resistance are driven by interactions between the tumour microenvironment and cancer cell plasticity. Phenotype-specific expression of the AXL receptor tyrosine kinase is key in cancer invasion and resistance to treatment, but how the ALX is activated has remained unclear.
Using melanoma as a model, the Goding research group and collaborators at University Rey Juan Carlos show that AXL is activated by exposure to human adipocytes and to oleic acid, a fatty acid abundant in lymph and adipocytes. The activation of AXL triggers formation and translocation of a β-catenin-CAV1 complex required for melanoma invasiveness.
Of particular note, only undifferentiated, high in AXL melanoma cells engage in symbiosis with human adipocytes, leading to AXL-dependent fatty acid uptake and nuclear localisation of the β-catenin-CAV1 complex. These results demonstrate an AXL and CAV-1 dependent mechanism by which a nutritional input drives phenotype-specific activation of a pro-metastasis program.
Given the key role of AXL in a wide range of cancers, the results offer major insights into the mechanisms of cancer cell dormancy and therapy resistance.
To read more, please see the full article in Genes & Development