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Molecular mechanisms of epithelial–mesenchymal transition

2014; Nature Portfolio; Volume: 15; Issue: 3 Linguagem: Inglês

10.1038/nrm3758

1471-0080

Samy Lamouille, Jian Xu, Rik Derynck,

TGF-β signaling in diseases

Epithelial–mesenchymal transition (EMT) is integral to development and pathology. This switch in cell differentiation and behaviour requires key transcription factors, including SNAIL, zinc-finger E-box-binding (ZEB) and basic helix–loop–helix transcription factors, and is regulated by several signalling pathways, including those mediated by the transforming growth factor-β (TGFβ) family. The transdifferentiation of epithelial cells into motile mesenchymal cells, a process known as epithelial–mesenchymal transition (EMT), is integral in development, wound healing and stem cell behaviour, and contributes pathologically to fibrosis and cancer progression. This switch in cell differentiation and behaviour is mediated by key transcription factors, including SNAIL, zinc-finger E-box-binding (ZEB) and basic helix–loop–helix transcription factors, the functions of which are finely regulated at the transcriptional, translational and post-translational levels. The reprogramming of gene expression during EMT, as well as non-transcriptional changes, are initiated and controlled by signalling pathways that respond to extracellular cues. Among these, transforming growth factor-β (TGFβ) family signalling has a predominant role; however, the convergence of signalling pathways is essential for EMT.