RNA-seq data of primary murine mammary epithelium from 3 CMV::rtTA;TRE-Twist1 mice and 3 TRE-Twist1 littermates, cultured for 24 h in basal medium and then 48 h in medium with doxycycline. Mus musculus

Dissemination of epithelial cells is a critical step in metastatic spread. Molecular models of dissemination focus on loss of E-cadherin or repression of cell adhesion through an epithelial to mesenchymal transition (EMT). We sought to define the minimum molecular events necessary to induce dissemination of cells out of primary murine mammary epithelium. Deletion of E-cadherin disrupted epithelial architecture and morphogenesis but only rarely resulted in dissemination. Conversely, expression of the EMT transcription factor Twist1 induced rapid dissemination of cytokeratin-positive epithelial cells. Twist1 induced dramatic transcriptional changes in the extracellular compartment and in cell-matrix adhesion genes but not in cell-cell adhesion genes. Surprisingly, we observed disseminating cells with membrane localized E-cadherin and β-catenin, and E-cadherin knockdown strongly inhibited Twist1-induced single cell dissemination. Our data reveal that dissemination can occur with retention of epithelial cell identity and represents a transition between collective and individually migratory epithelial phenotypes.