Lamouille 2014: molecular mechanisms of epithelial-mesenchymal transition
The detailed molecular account of how cells switch from a fixed epithelial state to a mobile mesenchymal one, from the TGF-beta signals that start it to the transcription factors, microRNAs and cytoskeletal changes that carry it out.
Overview
Lamouille, Xu and Derynck reviewed the machinery of epithelial-mesenchymal transition: TGF-beta signalling through SMAD and non-SMAD routes as the best-characterised trigger, the core transcription factors Snail, ZEB and Twist that repress E-cadherin and epithelial genes, the miR-200 and miR-34 families that hold those factors in check, and the changes in junctions, polarity and actin cytoskeleton that produce motility and invasion. They stressed that EMT is often partial and reversible, with cells occupying intermediate states, and described how the programme is co-opted in fibrosis and cancer.
- TGF-beta is the best-characterised EMT inducer, acting through SMAD-dependent and independent pathways alongside Wnt, Notch and growth factor signals.
- Snail, ZEB and Twist transcription factors repress E-cadherin and drive the mesenchymal programme; miR-200 and miR-34 microRNAs oppose them in feedback loops.
- EMT is frequently partial and reversible, producing hybrid cell states.
This is the reference for the mechanics behind invasion and metastasis and for why partial EMT states, rather than a full switch, are now thought to matter most in cancer. It also explains the appeal and the difficulty of drugging EMT, since its drivers are transcription factors.
- A review, largely of cell culture and developmental systems.
- Direct evidence for EMT in human metastasis remains harder to obtain than in models.
Similar pages
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