Abstract 3308: Axl is required for EMT-induced stem cell traits and metastasis in breast cancer

Epithelial-to-mesenchymal transition (EMT) endows carcinoma cells with migratory, survival and stem cell-like attributes that facilitate metastasis. We have shown that expression of the receptor tyrosine kinase Axl in primary breast cancer is a strong independent predictor of poor overall survival and is further enhanced in matched patient metastases. Axl is upregulated by EMT-induction in mammary epithelial cells and establishes an autocrine signaling loop with its ligand, Gas6. Axl signaling is required to maintain the mesenchymal and stem cell-like phenotype induced by EMT-transcription factors. Axl-inhibition downregulated mesenchymal and stem cell marker expression, blocked invasiveness, inhibited mammosphere formation and reversed drug resistance. Axl knockdown completely prevented the spread of metastatic breast carcinoma cells from the mammary gland and increased overall survival in two different orthotopic breast cancer models. Axl was also required for breast cancer cells to extravasate into the lung following intravenous injection. These results suggest that Axl signaling is necessary for metastasis, stem cell and therapy resistance traits in breast cancer. Hence, Axl-inhibition represents a novel therapeutic opportunity to target stem-like and drug resistant breast cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3308. doi:1538-7445.AM2012-3308