Epithelial-mesenchymal transition (EMT) describes a morphogenetic program which confers mesenchymal cell properties such as reduced cell-cell contact and increased cell migration and invasion, to epithelial cells. Here we investigate the role of the pleiotropic transcription/splicing factor and RNA-binding protein nuclease-sensitive element-binding protein 1 (YBX1/YB-1) in inducing EMT and increasing the oncogenic potential of epithelial MDCK cells. Stable expression of YBX1 in MDCK cells (MDCK^YBX1) induced partial EMT, including cytosolic relocalization of E-cadherin, increased cell scattering, and anchorage-independent growth. A critical feature of this study was the observation that MDCK^YBX1 cells were pro-oncogenic and established tumour xenograft growth, in contrast to parental MDCK/ MDCK^vec cells. We further sought to identify the molecules that may confer these properties, and used an in-depth proteomic approach (UPLC Orbitrap Elite, MaxQuant workflow) to profile and quantitate (label-free quantitation) the cell lines from in vitro cell culture (cellular and secreted molecules), as well as the in vivo MDCK^YBX1 cell tumour xenograft directly. We reveal that YBX1 regulates the extracellular environment through expression levels of secreted/ extracellular proteins. The increased tumourigenicity of MDCK^YBX1 cells correlated with the identification of elevated levels of secreted factors (TGF-β, CSF-1, NGF, and VGF) and proteases (ADAM9 and ADAM17), known to enhance angiogenesis and cancer progression. Treatment of recipient 2F-2B endothelial cells with MDCK^YBX1 cell conditioned medium containing both soluble proteins and extracellular vesicles increased their motility. These findings contribute to our understanding of how YBX1 as an oncogenic enhancer mediates partial EMT in epithelial cells and promotes tumour angiogenesis via the elevated release of a new suite of secreted molecules.