Mesenchymal to epithelial transition (MET) is a process that converts motile mesenchymal cells to polarized epithelial cells, and this physiological example of cell plasticity occurs frequently during embryogenesis. During kidney development, MET is thought to be induced by BMP-7 to produce the absorptive epithelial cells that line the nephron. MET can also be induced in vitro by E-Cadherin overexpression, FGF Receptor 2 isoform switching, and EGF R inhibition. Consistent with the hypothesis that MET represents a reversion of epithelial to mesenchymal transition (EMT), downregulation of EMT-inducing transcription factors such as Snail, Slug, and ZEB1 are associated with MET.
Increasing evidence indicates that EMT/MET pathways may regulate epithelial carcinogenesis in vivo. Specifically, EMT pathways are hypothesized to facilitate tumor cell dissociation, intravasation, and migration during the early stages of metastasis, while MET is thought to give rise to a metastatic lesion with cellular characteristics of the original tumor. Tumor cell grafting experiments revealed that only tumor cells expressing high levels of the epithelial markers E-Cadherin and Cytokeratin form metastases. In response to localized cues, such as signals secreted from recruited cells of the immune system, cancer cells may activate MET pathways and contribute to metastatic tumor formation. Other hypotheses state that EMT maintenance is lost when metastatic cells migrate away from the primary tumor and the cells subsequently undergo MET and revert to an epithelial state.