How epithelial cells shed their junctions and become mobile, the transcription factors that drive it, the marker switch you can see on immunohistochemistry, and why it matters for invasion, metastasis and drug resistance.
- What it is: epithelial cells lose polarity and cell–cell junctions and gain a migratory, mesenchymal phenotype
- Drivers: transcription factors SNAIL, SLUG (SNAI2), TWIST and ZEB1/2, induced by TGF-β, Wnt, Notch and hypoxia
- Marker switch: E-cadherin and cytokeratin fall; N-cadherin, vimentin and fibronectin rise
- In cancer: promotes invasion, metastasis, stem-cell properties and therapy resistance
- Reverse process: mesenchymal–epithelial transition (MET) helps metastases grow at distant sites
Three types of EMT
| Type | Setting | Example |
|---|---|---|
| Type 1 | Embryogenesis | Gastrulation, neural crest migration, heart valve formation |
| Type 2 | Wound healing and fibrosis | Renal tubular and lung fibrosis after injury |
| Type 3 | Cancer progression | Invasive front of carcinomas, sarcomatoid change |
Molecular drivers and markers
| Lost (epithelial) | Gained (mesenchymal) |
|---|---|
| E-cadherin, cytokeratins, claudins, occludin, ZO-1, apical–basal polarity | N-cadherin (cadherin switch), vimentin, fibronectin, smooth muscle actin, matrix metalloproteinases, motility |
SNAIL, SLUG and ZEB proteins bind E-boxes in the E-cadherin (CDH1) promoter and repress it; TWIST cooperates and also promotes N-cadherin. Upstream signals include TGF-β, Wnt/β-catenin, Notch, Hedgehog, growth factor receptors and hypoxia (HIF-1α).
EMT is usually partial and reversible. Cells at the invasive front may show hybrid features, and after seeding a distant site many revert to an epithelial phenotype (MET), which is why metastases often look like the primary.
Pathology MCQEMT in tumours
- Invasion and metastasis: loss of adhesion and gain of motility and proteases let cells break through basement membrane and enter vessels.
- Stemness and resistance: EMT programmes are linked to cancer stem cell features and resistance to chemotherapy and targeted therapy.
- Morphological correlates: sarcomatoid (spindle cell) carcinomas, metaplastic breast carcinoma, carcinosarcoma and tumour budding at the invasive front.
- Not every E-cadherin loss is EMT: lobular breast carcinoma loses E-cadherin through CDH1 mutation but keeps an epithelial phenotype.
A carcinoma that loses E-cadherin and keratin while gaining vimentin at its invasive edge is undergoing EMT. Remember the cadherin switch: E-cadherin down, N-cadherin up.
Practice questions
Which transcription factor represses E-cadherin during EMT?
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Which marker change is typical of EMT?
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Why do metastases often look epithelial like the primary carcinoma?
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- EMT: epithelial cells lose junctions and polarity and become motile.
- SNAIL, SLUG, TWIST and ZEB drive it; TGF-β is a key inducer.
- E-cadherin down, N-cadherin and vimentin up.
- EMT aids invasion; MET helps metastases grow.
Kumar V, Abbas AK, Aster JC. Robbins and Cotran Pathologic Basis of Disease, 10th ed. Elsevier; 2020 · Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest 2009;119:1420–1428 · Dongre A, Weinberg RA. New insights into the mechanisms of epithelial–mesenchymal transition and implications for cancer. Nat Rev Mol Cell Biol 2019;20:69–84
High-Yield, Board-Style Image MCQs & Interactive Whole Slide Images
High-resolution virtual microscopy with questions aligned to ABP, FRCPath, NEET-SS, DM Hematopathology and MD/DNB.
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