The Receptor Tyrosine Kinase AXL Is Required at Multiple Steps of the Metastatic Cascade During HER2-Positive Breast Cancer Progression

AXL is activated by its ligand GAS6 and is expressed in triple-negative breast cancer cells. In the current study, we report that AXL is also expressed in HER2 breast cancers where it correlates with poor patient survival. Using murine models of HER2 breast cancer, Axl, but not Gas6, was found to be essential for metastasis. We determined that AXL is required for intravasation, extravasation and growth at the metastatic site. AXL is expressed in HER2 cancers displaying EMT signatures where it contributes to sustained EMT. Interfering with AXL in a patient-derived xenograft impaired TGF-β-induced cell invasion. Lastly, pharmacological inhibition of AXL decreased the metastatic burden of mice developing HER2 breast cancer. Our data identify AXL as a potential anti-metastatic, co-therapeutic target for the treatment of HER2 breast cancers.