Figure 2.

Schema of invasion plasticity. In collective cell invasion, cells can maintain cell–cell attachments and invade collectively, harmonized as sheets or cell clusters. Epithelial–mesenchymal transformation (EMT) is a molecular mechanism characterized by the loss of polarity of epithelial cells, which disrupts cell attachment to the extracellular matrix (ECM). EMT leads to increased invasion capacity and histologically acquires a more mesenchymal phenotype, which represents an elongated, spindle-like cell shape with the formation of pseudopod protrusions and filopodia. Alternatively, by losing dependence on ECM and by promoting actomyosin contractility, mesenchymal cells can undergo a mesenchymal–amoeboid transition (MAT) and invade in the amoeboid mode. MAT in malignant cells can be induced by decreased cell–ECM interaction, loss of ECM proteolysis, enhanced contractility, the blockade of Rac activity, or indirectly promoting Rho/ROCK activation. The amoeboid and mesenchymal modes of invasion are often inter-convertible, and amoeboid cells can also revert to mesenchymal mode by amoeboid–mesenchymal transition (AMT). Important mediators of these transition changes in expression are described.