Epithelial-mesenchymal transition (EMT) is a morphogenic process involving an orchestrated series of transcriptional reprogramming events leading to loss of epithelial characteristics and gain of mesenchymal properties. This transition involves a shift in cellular plasticity, and encompasses diverse alterations to epithelial cell morphology, diminished polarity, cytoskeletal reorganization, and enhanced motility and invasiveness. Previously, we examined the contribution of the secretome in the EMT process. For example, MS-based secretome studies, using oncogenic H-Ras transformed MDCK cells (21D1 cells) as a model, revealed that upon EMT there is diminished release into the extracellular environment (i.e., the secretome) of cell-cell and cell-matrix proteins (Mathias et al., 2010 PMID: 19954229) which normally restrict cellular movement and provide cell-cell/matrix adhesion. Moreover, H-Ras transformation was accompanied by elevated secretion of proteases and factors that promote cell motility. We next studied the contribution of EVs (e.g., exosomes) during oncogenic H-Ras induced EMT. Significant findings were the enrichment of key subunits of the splicing complex, transcriptional factors such as the master transcriptional regulator YBX1, and matrix metalloproteinases (e.g., MMP1) in exosomes upon H-Ras induced EMT (Tauro et al 2013 PMID: 23645497).We next questioned whether overexpression of YBX1 alone in MDCK cells could induce EMT. To this end we stably transfected YBX1 in MDCK cells (MDCKYBX1) using pcDNA3.1(+) vector containing the YBX1 gene under the control of a CMV promoter and an SV40-driven neomycin resistance plasmid gene. Ongoing studies directed towards ascertaining in vivo tumorogenicity of MDCKYBX1 cells and in vitro studies examining the functional role of MDCKYBX1 – Exos in human breast cancer model cell lines will be presented.