Abstract LB-108: Formation and maintenance of mesenchymal and stem-cell states in the breast by paracrine and autocrine signals

Abstract

Abstract Passage through an epithelial-mesenchymal transition (EMT) is associated with the acquisition of migratory and self-renewal abilities in human mammary epithelial cells (MECs). The signaling mechanisms that induce and then maintain these properties have remained unclear. We describe three signaling pathways, involving Transforming Growth Factor (TGF)-beta as well as canonical and non-canonical Wnt signaling, that collaborate to induce epithelial MECs to enter into a mesenchymal and SC-like state. Acting as autocrine signaling loops, these pathways then maintain migratory and self-renewal abilities in normal MECs and control tumorigenicity and metastasis in their transformed derivatives. Autocrine signaling is enabled, at least in part, through downregulation of secreted Wnt antagonists and Bone Morphogenetic Proteins. Like immortalized and transformed MECs, the maintenance of migratory and self-renewal abilities in primary human MECs is dependent on these autocrine loops, suggesting that similar mechanisms regulate biological properties of normal tissue stem cells and tumor-initiating cells in the breast Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-108. doi:10.1158/1538-7445.AM2011-LB-108