Thiery 2002: epithelial-mesenchymal transitions in tumour progression
The review that brought the developmental idea of epithelial-mesenchymal transition into cancer biology, proposing it as the mechanism by which carcinoma cells detach, invade and travel to distant sites.
Overview
Thiery reviewed the evidence that carcinomas use an epithelial-mesenchymal transition to progress: loss of E-cadherin-based junctions, cytoskeletal remodelling and gain of migratory behaviour, driven by signals including TGF-beta, receptor tyrosine kinases, Wnt and the transcription factors Snail and Twist. He drew the parallel with gastrulation and neural crest migration in embryos and argued that EMT, and its reversal at secondary sites, could account for how metastases arise and why they often look epithelial again.
- Carcinoma progression involves loss of E-cadherin and epithelial polarity with gain of mesenchymal, migratory features.
- The same signalling pathways and transcription factors drive EMT in embryos and in tumours.
- Proposed EMT and its reversal as the basis of invasion and distant metastasis.
This is the paper that made EMT a cancer concept, cited by almost every metastasis study since. It set the research agenda that later produced the EMT stem cell link and current work on partial EMT states.
- Largely based on cell culture and developmental analogies at the time.
- Direct evidence for EMT in human metastasis has remained harder to obtain than the model predicts.
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.
EMT is the most cited explanation for how carcinomas invade and spread and for part of their drug resistance. This primer is the entry point for the field, and its framework informs current work on partial EMT states, circulating tumour cells and therapies aimed at the transition.
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