How Much Do We Know about Cancer Cells? Epithelial-mesenchymal Transition

The epithelial-mesenchymal transition (EMT) describes a rapid and often reversible modulation of phenotype by epithelial cells. EMT was originally defined in the context of developmental stages, including heart morphogenesis, mesoderm and neural crest formation. Epithelial cells loosen cell-cell adhesion structures throughout EMT. They modulate their polarity, cytoskeleton organization and typically express vimentin filaments and downregulate cytokeratins. They become isolated, mobile and resistant to anoikis. The epithelial-mesenchymal transition at least superficially resembles the evolution from normal to transformed cell phenotype during carcinoma progression. The relevance of the concept of epithelial-mesenchymal transition in this context was suggested by in vitro models using transformed epithelial cells. Transduction pathways typical for embryogenic EMT in vivo were also found to be activated during cancer progression. More recently, it has been found that such pathways suggest an increased plasticity linked to cellular stemness and ability to generate tumors. However, in the absence of direct evidence, a number of oncologists and pathologists remain skeptical about applying the EMT concept to human tumor progression. In fact, EMT concept appears to be fully relevant in some situations, but the concept has to be adjusted in other situations to reflect tumor cell renewal and plasticity during carcinoma progression and metastasis. 1) EMT semantics. EMT consists of a rapid and often reversible change of cell phenotype. Epithelial cells loosen cell-cell adhesion structures including adherens junctions and desmosomes, modulate their polarity and rearrange their cytoskeleton: intermediate filaments typically switch from cytokeratins to vimentin. Cells become isolated, motile, and resistant to apoptosis. The epithelial-mesenchymal transition was initially defined as the cellular remodeling occuring during heart morphogenesis, but the concept was extended to analogous transformation occuring during the formation of mesoderm and neural crest [1, 2]. In the last twenty years, EMT has been studied in in se rm -0 06 36 09 1, v er si on 1 26 O ct 2 01 1 Author manuscript, published in "Annals of Oncology 2010;21 Suppl 7:vii89-92" DOI : 10.1093/annonc/mdq292