Epithelial–mesenchymal Transitions in Tumour Progression

Key Points Epithelial–mesenchymal transition (EMT) is a highly conserved and fundamental process that governs morphogenesis in multicellular organisms. There is good evidence that EMT gives rise to the dissemination of single carcinoma cells from the sites of the primary tumours. More generally, EMT might be involved in the dedifferentiation programme that leads to malignant carcinoma. Recent research conducted in embryonic model systems and in normal and transformed cell lines has identified several signal-transduction pathways for EMT, including the activation of several receptor tyrosine kinases and transforming growth factor-β receptors. Transcriptional repressors of the E-cadherin gene are activated downstream in these pathways, leading to the loss of the epithelial phenotype. Other effectors of the EMT can modulate other adhesion systems and trigger the remodelling of the actin cytoskeleton, leading to the mesenchymal phenotype and the scattering of carcinoma cells. Potential drug targets of EMT in carcinoma are now in development: inhibitors of receptor tyrosine kinases are in Phase III clinical trials. These drugs might have a considerable impact on the long-term survival of people diagnosed with cancer.