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How a cancer cell changes shape to migrate and to shrug off drugs. Transcription factors like ZEB1 and SNAIL loosen the cell, switch on pumps that eject chemotherapy, and hide it from the immune system.
TGF-β, Wnt, Notch, hypoxia, and inflammation induce ZEB1/2, SNAIL, SLUG, TWIST, which repress E-cadherin and epithelial genes and induce vimentin, N-cadherin, and matrix proteases. EMT confers invasiveness, stemness, resistance to apoptosis, upregulated ABC efflux transporters (ABCB1/P-gp, ABCG2), and immune exclusion. Partial EMT states dominate in tumours. Clinically: the mesenchymal/claudin-low TNBC subtype, sarcomatoid carcinomas, and TKI resistance (EGFR NSCLC). No approved EMT drug; strategies include TGF-β blockade (bintrafusp failed), efflux-agnostic payloads, and targeting mesenchymal-state dependencies (GPX4, ferroptosis).
A brick in a wall (epithelial cell) turning into a nomad: it lets go of its neighbours, packs pumps to spit out poison, and puts on camouflage. The wall-brick was easy to hit; the nomad is not.
It gives the PD-L1-negative mesenchymal subtype, the group immunotherapy leaves behind, a mechanistic route back to immune visibility, and explains why immune infiltration and subtype are coupled.
It means a CMS4 call on a bulk sample partly measures how much stroma was in the block, which is both a caution for the classification and a pointer to the stroma as the thing to treat.
Together with the negative HALO-301 trial of hyaluronidase this ended the first, blunt version of stromal targeting; second-generation ideas aim to reprogramme rather than remove the stroma.
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.
The vocabulary used on the triple-negative page (basal-like 1 and 2, mesenchymal, luminal androgen receptor, immunomodulatory) comes from this paper; it made triple-negative breast cancer several diseases with several possible drugs rather than one disease with none.
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.
This paper is why metastasis, stemness and therapy resistance are now studied as one problem. It suggests that the cells most able to spread are also the ones most able to regrow, and it motivates therapies that target the mesenchymal or stem-like state.
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.
Shares Lamouille 2014: molecular mechanisms of epithelial-mesenchymal transition, Thiery 2002: epithelial-mesenchymal transitions in tumour progression, Invasive, Kalluri and Weinberg 2009: the basics of epithelial-mesenchymal transition.
Shares Stromal contribution to the colorectal cancer transcriptome, Soften the tissue that new metastases need in order to grow, Reprogramme the stroma rather than remove it: second-generation stromal trials with a stromal biomarker and a survival endpoint, Classical versus basal-like (squamous) subtypes of pancreatic cancer, and GATA6.
Shares Stromal contribution to the colorectal cancer transcriptome, Hippo-YAP/TAZ, Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival, Invasion: proteases, adhesion & the invasive front.
Shares Reprogramme the stroma rather than remove it: second-generation stromal trials with a stromal biomarker and a survival endpoint, Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival, Invasion: proteases, adhesion & the invasive front, TGF-β signalling.
Shares Erik Sahai, Reprogramme the stroma rather than remove it: second-generation stromal trials with a stromal biomarker and a survival endpoint, Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival, Invasion: proteases, adhesion & the invasive front.
Shares Max S. Wicha, Mani 2008: the epithelial-mesenchymal transition generates cells with properties of stem cells, Cancer stem cell theory and phenotypic plasticity, Triple-negative breast cancer (TNBC).
Shares Cheap perioperative beta-blocker plus anti-inflammatory to blunt surgical stress, Soften the tissue that new metastases need in order to grow, Strip the platelet coat off travelling tumour cells in ctDNA-positive patients, Metastasis is understood least and studied last.
Shares Claudin-low breast cancer, Mesenchymal triple-negative breast cancer (M), Classical versus basal-like (squamous) subtypes of pancreatic cancer, and GATA6, Triple-negative breast cancer (TNBC).