{"entity":{"id":"emt","kind":"pathway","name":"Epithelial-mesenchymal transition & drug efflux","aka":[],"tldr":"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.","summary":"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).","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Epithelial–mesenchymal_transition","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Epithelial–mesenchymal_transition"}],"tags":[],"related":["theories-of-cancer","cancer-stem-cell-theory"],"cancers":["tnbc","nsclc"],"sections":[],"technologies":["adc","radioligand-therapy","single-cell-spatial"],"targets":["trop2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["efflux-pump","resistance"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-lamouille-emt-molecular-mechanisms-nrmcb-2014"],"journals":[],"dependsOn":[],"notes":[],"analogy":"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.","nodes":[{"id":"tgf","label":"TGF-β, Wnt, Notch, hypoxia","x":50,"y":5},{"id":"tf","label":"ZEB1/2, SNAIL, TWIST","x":50,"y":25},{"id":"ecad","label":"E-cadherin, claudins","x":20,"y":48},{"id":"vim","label":"Vimentin, N-cadherin, MMPs","x":80,"y":48},{"id":"abc","label":"ABCB1 / ABCG2 efflux","x":20,"y":72},{"id":"stem","label":"Stemness, apoptosis resistance","x":50,"y":72},{"id":"imm","label":"Immune exclusion","x":80,"y":72},{"id":"out","label":"Invasion, metastasis, drug resistance","x":50,"y":95}],"edges":[{"from":"tgf","to":"tf","type":"activates"},{"from":"tf","to":"ecad","type":"inhibits"},{"from":"tf","to":"vim","type":"activates"},{"from":"tf","to":"abc","type":"activates"},{"from":"tf","to":"stem","type":"activates"},{"from":"tf","to":"imm","type":"activates"},{"from":"vim","to":"out","type":"activates"},{"from":"abc","to":"out","type":"activates"},{"from":"stem","to":"out","type":"activates"}],"interventions":["No approved direct EMT inhibitor","Payloads with low efflux susceptibility (sac-TMT's belotecan derivative claims this) and radiation (efflux-independent)","TGF-β pathway blockade (mostly failed so far)","Ferroptosis inducers for mesenchymal-state cells (preclinical)","Immune approaches to overcome exclusion (STING, radiation)"]},"route":"/pathways/emt/","neighbours":{"pathway":[{"id":"basement-membrane-tissue-barriers","kind":"pathway","name":"Basement membrane & tissue barriers","route":"/pathways/basement-membrane-tissue-barriers/"},{"id":"bladder-cancer-signalling","kind":"pathway","name":"Bladder cancer (KEGG map)","route":"/pathways/bladder-cancer-signalling/"},{"id":"cancer-stem-cells-plasticity","kind":"pathway","name":"Cancer stem cells & phenotypic plasticity","route":"/pathways/cancer-stem-cells-plasticity/"},{"id":"drug-efflux-pumps","kind":"pathway","name":"Drug efflux pumps (ABC transporters)","route":"/pathways/drug-efflux-pumps/"},{"id":"ferroptosis-cell-death","kind":"pathway","name":"Ferroptosis & regulated cell death","route":"/pathways/ferroptosis-cell-death/"},{"id":"gastric-cancer-signalling","kind":"pathway","name":"Gastric cancer (KEGG map)","route":"/pathways/gastric-cancer-signalling/"},{"id":"hippo-yap","kind":"pathway","name":"Hippo-YAP/TAZ","route":"/pathways/hippo-yap/"},{"id":"intravasation-ctc-survival","kind":"pathway","name":"Intravasation & circulating tumour cells","route":"/pathways/intravasation-ctc-survival/"},{"id":"invasion-ecm-degradation","kind":"pathway","name":"Invasion: proteases, adhesion & the invasive front","route":"/pathways/invasion-ecm-degradation/"},{"id":"proteoglycans-in-cancer","kind":"pathway","name":"Proteoglycans in cancer","route":"/pathways/proteoglycans-in-cancer/"},{"id":"tgf-beta","kind":"pathway","name":"TGF-β signalling","route":"/pathways/tgf-beta/"},{"id":"metastatic-cascade","kind":"pathway","name":"The metastatic cascade","route":"/pathways/metastatic-cascade/"},{"id":"theories-of-cancer","kind":"pathway","name":"Theories of cancer: how the ideas connect","route":"/pathways/theories-of-cancer/"},{"id":"thyroid-cancer-signalling","kind":"pathway","name":"Thyroid cancer (KEGG map)","route":"/pathways/thyroid-cancer-signalling/"},{"id":"tumor-microenvironment","kind":"pathway","name":"Tumour microenvironment (TME)","route":"/pathways/tumor-microenvironment/"}],"term":[{"id":"cancer-stem-cell-theory","kind":"term","name":"Cancer stem cell theory and phenotypic plasticity","route":"/terms/cancer-stem-cell-theory/"},{"id":"classical-vs-basal-like","kind":"term","name":"Classical versus basal-like (squamous) subtypes of pancreatic cancer, and GATA6","route":"/terms/classical-vs-basal-like/"},{"id":"claudin-low","kind":"term","name":"Claudin-low breast cancer","route":"/terms/claudin-low/"},{"id":"cms-subtypes","kind":"term","name":"Consensus molecular subtypes (CMS1-4)","route":"/terms/cms-subtypes/"},{"id":"efflux-pump","kind":"term","name":"Drug efflux pumps (ABC transporters)","route":"/terms/efflux-pump/"},{"id":"resistance","kind":"term","name":"Drug resistance (primary and acquired)","route":"/terms/resistance/"},{"id":"unlocking-phenotypic-plasticity","kind":"term","name":"Hallmark (2022): unlocking phenotypic plasticity","route":"/terms/unlocking-phenotypic-plasticity/"},{"id":"activating-invasion-metastasis","kind":"term","name":"Hallmark: activating invasion and metastasis","route":"/terms/activating-invasion-metastasis/"},{"id":"invasive-cancer","kind":"term","name":"Invasive","route":"/terms/invasive-cancer/"}],"cancer":[{"id":"tnbc-mesenchymal-stem-like","kind":"cancer","name":"Mesenchymal stem-like triple-negative breast cancer (MSL)","route":"/cancers/tnbc-mesenchymal-stem-like/"},{"id":"tnbc-mesenchymal","kind":"cancer","name":"Mesenchymal triple-negative breast cancer (M)","route":"/cancers/tnbc-mesenchymal/"},{"id":"metaplastic-breast-carcinoma","kind":"cancer","name":"Metaplastic breast carcinoma","route":"/cancers/metaplastic-breast-carcinoma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"},{"id":"pancreatic-undifferentiated-carcinoma-ogc","kind":"cancer","name":"Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells","route":"/cancers/pancreatic-undifferentiated-carcinoma-ogc/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"radioligand-therapy","kind":"technology","name":"Radioligand therapy (beta emitters)","route":"/technologies/radioligand-therapy/"},{"id":"single-cell-spatial","kind":"technology","name":"Single-cell & spatial profiling","route":"/technologies/single-cell-spatial/"}],"target":[{"id":"abcb1","kind":"target","name":"ABCB1","route":"/targets/abcb1/"},{"id":"abcg2","kind":"target","name":"ABCG2","route":"/targets/abcg2/"},{"id":"trop2","kind":"target","name":"TROP2","route":"/targets/trop2/"},{"id":"zeb1","kind":"target","name":"ZEB1","route":"/targets/zeb1/"}],"paper":[{"id":"paper-ozdemir-caf-depletion-accelerates-pancreatic-cancer-cancer-cell-2014","kind":"paper","name":"Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival","route":"/key-papers/paper-ozdemir-caf-depletion-accelerates-pancreatic-cancer-cancer-cell-2014/"},{"id":"paper-lehmann-tnbc-subtypes-jci-2011","kind":"paper","name":"Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies","route":"/key-papers/paper-lehmann-tnbc-subtypes-jci-2011/"},{"id":"paper-kalluri-weinberg-emt-basics-jci-2009","kind":"paper","name":"Kalluri and Weinberg 2009: the basics of epithelial-mesenchymal transition","route":"/key-papers/paper-kalluri-weinberg-emt-basics-jci-2009/"},{"id":"paper-lamouille-emt-molecular-mechanisms-nrmcb-2014","kind":"paper","name":"Lamouille 2014: molecular mechanisms of epithelial-mesenchymal transition","route":"/key-papers/paper-lamouille-emt-molecular-mechanisms-nrmcb-2014/"},{"id":"paper-mani-emt-stem-cell-properties-cell-2008","kind":"paper","name":"Mani 2008: the epithelial-mesenchymal transition generates cells with properties of stem cells","route":"/key-papers/paper-mani-emt-stem-cell-properties-cell-2008/"},{"id":"paper-lehmann-tnbc-subtype-multiomics-nat-commun-2021","kind":"paper","name":"Multi-omics analysis identifies therapeutic vulnerabilities in triple-negative breast cancer subtypes","route":"/key-papers/paper-lehmann-tnbc-subtype-multiomics-nat-commun-2021/"},{"id":"paper-isella-stromal-contribution-colorectal-transcriptome-nat-genet-2015","kind":"paper","name":"Stromal contribution to the colorectal cancer transcriptome","route":"/key-papers/paper-isella-stromal-contribution-colorectal-transcriptome-nat-genet-2015/"},{"id":"paper-thiery-emt-tumour-progression-nrc-2002","kind":"paper","name":"Thiery 2002: epithelial-mesenchymal transitions in tumour progression","route":"/key-papers/paper-thiery-emt-tumour-progression-nrc-2002/"}],"roadmap":[{"id":"tnbc-history","kind":"roadmap","name":"TNBC roadmap: from 'nothing to target' to ADC + immunotherapy first line","route":"/roadmaps/tnbc-history/"},{"id":"tnbc-roadmap","kind":"roadmap","name":"Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem","route":"/roadmaps/tnbc-roadmap/"}],"idea":[{"id":"idea-bio2-perioperative-betablocker-nsaid","kind":"idea","name":"Cheap perioperative beta-blocker plus anti-inflammatory to blunt surgical stress","route":"/ideas/idea-bio2-perioperative-betablocker-nsaid/"},{"id":"idea-efflux-agnostic","kind":"idea","name":"Efflux-agnostic therapy for mesenchymal TNBC","route":"/ideas/idea-efflux-agnostic/"},{"id":"idea-ferroptosis-persisters","kind":"idea","name":"Kill drug-tolerant persisters through ferroptosis","route":"/ideas/idea-ferroptosis-persisters/"},{"id":"idea-reg-losartan-pancreatic-stroma","kind":"idea","name":"Losartan to loosen the stroma of pancreatic cancer before chemotherapy: a phase 3","route":"/ideas/idea-reg-losartan-pancreatic-stroma/"},{"id":"idea-pdac-stromal-reprogramming-not-depletion","kind":"idea","name":"Reprogramme the stroma rather than remove it: second-generation stromal trials with a stromal biomarker and a survival endpoint","route":"/ideas/idea-pdac-stromal-reprogramming-not-depletion/"},{"id":"idea-bio2-matrix-stiffness-prevention","kind":"idea","name":"Soften the tissue that new metastases need in order to grow","route":"/ideas/idea-bio2-matrix-stiffness-prevention/"},{"id":"idea-bio2-platelet-cloak-aspirin-mrd","kind":"idea","name":"Strip the platelet coat off travelling tumour cells in ctDNA-positive patients","route":"/ideas/idea-bio2-platelet-cloak-aspirin-mrd/"}],"person":[{"id":"andreas-trumpp","kind":"person","name":"Andreas Trumpp","route":"/people/andreas-trumpp/"},{"id":"erik-sahai","kind":"person","name":"Erik Sahai","route":"/people/erik-sahai/"},{"id":"max-wicha","kind":"person","name":"Max S. Wicha","route":"/people/max-wicha/"}],"bottleneck":[{"id":"b-metastasis-biology","kind":"bottleneck","name":"Metastasis is understood least and studied last","route":"/bottlenecks/b-metastasis-biology/"}]}}