Abstract C76: Axl signaling is required for stem cell traits and metastasis in breast cancer

Abstract

Abstract Epithelial-to-mesenchymal transition (EMT) endows carcinoma cells with migratory, survival and stem cell-like attributes that facilitate therapeutic resistance and metastasis. Expression of the Axl receptor tyrosine kinase in breast cancer correlates with EMT, poor survival and is prevalent in patient metastases. Axl upregulation in mammary epithelial cells by EMT-transcription factors, TGFbeta or hypoxia, establishes an autocrine-signaling loop with its ligand, Gas6. Inhibition of Axl signaling blocks EMT/ cancer stem cell traits including invasiveness, drug resistance, mammosphere formation, in vivo tumor initiation, and prevents spontaneous metastasis in orthotopic breast cancer models. Congruently, we show that Axl is expressed on mammary epithelial stem/progenitor cells and regulates multipotent progenitor activity. Thus Axl signal transduction represents a novel regulatory pathway linking normal mammary stem/progenitor cells and breast cancer stem cell activity. Clinical Axl-inhibitors represent a novel therapeutic opportunity to treat aggressive breast cancer. Citation Format: Crina Tiron, Fanny Pelissier, Katarzyna Wnuk-Lipinska, Ingunn Stefansson, Reeta Virtakoivu, Masaru Miyano, Tone Sandal, David Micklem, James Garbe, Martha Stampfer, Johanna Ivaska, Lars Akslen, Mark LaBarge, James Lorens. Axl signaling is required for stem cell traits and metastasis in breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr C76.