Figure 1

Basic molecular changes underlying EMT. A, Signaling along canonical TGF-β pathway activates EMT-promoting transcription factor (such as Twist, ZEB or Snail) to repress transcription of E-cadherin that initially forms the adherens junction (AJ) complex together with β-catenin. Extinction of E-cadherin from the AJ complex as well as concomitant phosphorylation via activated growth factor receptors lead to cytoplasmic accumulation and nuclear translocation of β-catenin, where it acts as a transcription factor for migration-associated genes. B, Enhanced expression of Vimentin in migrating tumor cells protects phosphorylated MAPK from cytoplasmic phosphatases, thus ensuring signaling activity along the EGFR/MAPK axis. This supports pro-migratory effects on the cytoskeleton (such as Rac-mediated actin polymerization) and secretion of lytic matrix metalloproteinases that cleave the surrounding extracellular matrix to allow for cell migration.