Figure 2.

Models for invasive migration in epithelial tumors. (A) The ‘classic’ epithelial to mesenchymal transition (EMT) can be induced by a variety of stimuli, both by genetic mutations within tumor epithelial cells (notably mutations in the p53 tumor suppressor), and by microenvironmental factors. When activated in epithelial cells, the EMT program orchestrates the simultaneous loss of epithelial characteristics and cell-cell adhesion and the gain of mobility and the ability to cross the basal membrane (BM). (B) TNFα-dependent alternative model to EMT. Drosophila epithelial cells with activated Ras oncogene and mutant for the scribble polarity tumor suppressor overproliferate to form tumor-like outgrowths. These mutant cells also loose epithelial polarity and display reduced cell-cell adhesion. However, in the absence of TNFα such cells do not migrate nor cross the basal membrane and proliferate in situ. Upon an inflammatory response from the host's blood cells (yellow), TNFα signaling stimulates basal membrane crossing and invasive migration. In this case, loss of polarity and adhesion are uncoupled from delamination and migration. These cells migrate as cohesive groups. Therefore, this paradigm appears independent of EMT. See the text for details.