Epithelial–mesenchymaltransition(EMT)isareversiblecellularprogrammethattransientlyplacesepithelialcellsintoquasi-mesenchymalcellstates1–4.Duringthisprocess,epithelialcellsprogressivelylosetheircobble-stoneepithelialappearanceinmonolayerculturestoadoptaspindle-shaped,mesenchymalmorphology.Theresultingmore-mesenchymalcellscanrevertbacktoanepithelialstateinthereverseprocess,knownasmesenchymal–epithelialtransition(MET)(FiG.1).EMThasimportantrolesinspecificstepsofembryogenesissuchasgastrulation,tissuemorphogenesisduringdevel-opmentandwoundhealingintheadult1,3,4.Moreover,themalignantprogressionofmanytypesofcarcinoma,quitepossiblyallofthem,dependsonEMTactivationinneoplasticcells5–7.Duringthecourseoftumourpro-gression,thispleiotropicprogrammeconfersonindi-vidualcarcinomacellsmultipletraitsassociatedwithhigh-grademalignancy6–10.Normally,thecellsthatformepithelialsheetsinvari-oustissuesofthebodydisplayapical–basalpolarityandareheldtogetherlaterallybytightjunctionsandadherensjunctions,thelatterofwhichareformedbycellsurfaceepithelialcadherin(E-cadherin)molecules.Thisorganizationiscrucialforthestructuralintegrityofepithelia.UponactivationofEMT,E-cadherinexpres-sionisrepressed,whichleadstothelossofthetypicalpolygonal,cobblestonemorphologyofepithelialcells.Thecellsacquireaspindle-shapedmesenchymalmor-phologyandexpressmarkersthatareassociatedwiththemesenchymalcellstate,notablyneuralcadherin(N-cadherin),vimentinandfibronectin3(FiG.1).EMTisorchestratedbyEMT-inducingtranscriptionsfactors(EMT-TFs),whichactpleiotropicallyandinvariouscombinationstoinducetheexpressionofgenesthatpro-motethemesenchymalcellstateandrepresstheexpres-sionofgenesthatmaintaintheepithelialstate1–4.DiverselinesofevidenceindicatethatEMTisorchestratedasanepigeneticprocessthatisnotdependentuponconcomi-tantDNAsequencealterationsinnormalandneoplasticcells11.Hence,likemanyotherbiologicalprogrammes,theexpressionofthisprogrammeanditswide-rangingeffectsontumourbiologycannotbedeterminedbysequencingcancercellgenomes...
