Paracrine and Systemic Signals That Induce Epithelial Cells to Enter into the Mesenchymal/Stem-Cell State

The epithelial-mesenchymal transition (EMT) represents a cell-biological program that enables both normal and neoplastic epithelial cells to acquire mesenchymal cell attributes, such as motility, invasiveness, and a resistance to apoptosis. At the same time, our work has revealed that epithelial cells that are forced through an EMT acquire many of the attributes of normal and neoplastic stem cells. This holds implications for the pathogenesis of metastasis, since carcinoma cells that have acquired mesenchymal attributes that enable them to physically disseminate also acquire the self-renewal trait that allows them to seed macroscopic metastases. To date our research has revealed a series of paracrine signals that impinge on epithelial cells and induces them to enter into an EMT. Long term exposure to these signals allow cells to remain in the mesenchymal/stem-cell state in a self-sustaining, metastable fashion.