The Ras and Src Signaling Cascades Involved in Epithelial Cell Scattering

Abstract

This contribution is to discuss key elements of the intracellular signaling cascades that bring about the cellular transformation referred to as epithelium-to-mesenchyme transition (EMT). EMT can be defined as the events that allows epithelial cells to dissociate from the tissue from which they originate and to migrate freely. EMT is therefore thought to play a fundamental role during the early steps of invasion and metastasis of carcinoma cells. Among biological agents which have been identified as inducers of EMT are a number of cytokines and extracellular matrix macromolecules. The coordinated changes in cell morphology, associated with the induction of cell motility and the disruption of intercellular junctions, are the consequence of signaling cascades emanating from the activation of the receptors specific for the inducing molecules and leading to changes in gene expression. Two of the transduction cascades that play a crucial role in the generation of EMT, namely the Src kinase family and the Ras signal, are discussed extensively with respect to their contribution of scattering signals.