The role of MEK signaling in driving mesenchymal transition in cell line models of human breast cancer metastasis

Epithelial to mesenchymal transition (EMT) is the process whereby sessile, polarised epithelial cells alter the expression of key adhesion and regulatory molecules, and gain the ability to survive and migrate as single cells. While this process occurs normally in development we now recognize that metastasis has many elements in common with developmental EMT, which is subverted by carcinoma cells to allow metastatic spread. Cancer cells rarely undergo a full conversion to them esenchymal phenotype, and instead appear to occupy a range of positions along a phenotypic spectrum between epithelial and mes-enchymal states. The Mitogen Activated Protein Kinase (MAPK) signaling cascade, which signals through MEK and ERK proteins, has previously been implicated in the regulation of EMT. In this work, we have used previously established breast cancer derived cell line models of epithelial-mesenchymal plasticity and applied RNA sequencing to measure transcriptional changes that occur as cells transition to a more mesenchymal phenotype. We have identified co-ordinated changes in the expression of genes in many, although not all, MEK-related signaling pathways, and delineated modulation in the abundance of key miRs implicated in breast cell differentiation and EMT. Collectively, our results demonstrate that different MEK related signaling pathways are altered by the induction of EMT in our cell line models, depending on the cell line’s initial position on the epithelial-mesenchymal spectrum, and the type of stimulus used to trigger transition