Key Protein in HER2+ Breast Cancer Found to Lead to Metastasis

A new study has found an underlying component that is responsible for breast cancer tumors becoming metastatic.

Researchers from Montréal found that HER2+ breast cancer tumor cells with elevated levels of the receptor tyrosine kinase AXL were more likely to progress towards metastases and that AXL correlates with poorer outcomes in patients with the disease. The study was published in Cell Reports.  

HER2+ breast cancer. (Source: Creative Commons)

“In the current study, we report AXL expression in HER2+ breast cancers where it correlates with poor patient survival. Using murine models of HER2+ breast cancer, AXL, but not its ligand Gas6, was found to be essential for metastasis,” the authors wrote.

“We determined that AXL is required for intravasation, extravasation, and growth at the metastatic site. We found that AXL is expressed in HER2+ cancers displaying epithelial-to-mesenchymal transition (EMT) signatures where it contributes to sustaining EMT. Interfering with AXL in a patient-derived xenograft (PDX) impaired transforming growth factor β (TGF-β)-induced cell invasion.”

The researchers performed the study on mice and used cells from cancer patients. They found that in women with HER2+ breast cancer, less AXL expression was linked to better survival rates. Previously, the researchers linked the protein to poor outcomes in patients with triple-negative breast cancer, but it was not examined in this study.

“Based on this discovery, a treatment targeting AXL could reduce the risk of metastasis,” Jean-François Côté, PhD, lead author of the study and director of the Research Axis in Cancer and Genetic Diseases in Montréal, said in a press release.

An AXL-inhibiting drug therapy, used by the researchers, was found to slow progression to metastasis in mice with HER2+ tumors. According to the authors, the drug is currently being tested in clinical trials.

“At the moment, we are checking whether the tumor’s environment, such as blood vessels and the immune system, is affected when AXL is inhibited,” Dr. Côté said.