REVIEWOncogenicrolesofEMT-inducingtranscriptionfactorsAlainPuisieux,ThomasBrabletzandJulieCaramelTheplasticityofcancercellsunderliestheircapacitytoadapttotheselectivepressurestheyencounterduringtumourdevelopment.Aberrantreactivationofepithelial–mesenchymaltransition(EMT),anessentialembryonicprocess,canpromotecancercellplasticityandfuelbothtumourinitiationandmetastaticspread.HerewediscusstherolesofEMT-inducingtranscriptionfactorsincreatingapro-tumorigenicsettingcharacterizedbyanintrinsicabilitytowithstandoncogenicinsultsthroughthemitigationofp53-dependentoncosuppressivefunctionsandthegainofstemness-relatedproperties.EMTisafundamentalembryonicprocessduringwhichpolarizedepithe-lialcellsconvertintomotilemesenchymalones.Thisreversibleprocessinvolvesprofoundchangesincellmorphologyandbehaviour,enablingcellstomoveintotheinterioroftheembryo,travellongdistances,andparticipateintheformationofinternalorgans1,2.TheactivationofthistransdifferentiationprogramdependsoncontextualmicroenvironmentalsignalsandisorchestratedbyanetworkofEMT-inducingtranscriptionfactors(EMT-TFs)thatinteractwithepigeneticregulatorstocontroltheexpressionofproteinsinvolvedincellpolarity,cell–cellcontact,cytoskel-etonstructureandextracellularmatrixdegradation(Fig.1),includingtherepressionofkeyepithelialgenes3.ThelossofE-cadherinexpressionisconsideredacrucialeventinEMT,andEMT-TFscanbeenclassifiedbasedontheirabilitytorepressE-cadherindirectlyorindirectly.Directrepressorsinclude:zincfingerproteinsoftheSNAILsuperfamily,suchasSNAI1(alsoknownasSNAIL),SNAI2(SLUG)andSNAI3(SMUC);zincfingerandE-boxbindingproteinsoftheZEBfamily,suchasZEB1(TCF8)andZEB2(SIP1);thebHLHfactorE47;andtheKrüppel-likefactorKLF8.FactorssuchastheTWISTbHLHproteins(TWIST1andTWIST2),thehomeoboxproteinsgoosecoid(GSC)andSIX1,thebHLHfactorE2.2andtheforkhead-boxproteinFOXC2repressE-cadherintranscriptionindirectly1.AlthoughEMTisthoughttobecomelatentinmostadulttissues,recentlinesofevidencesuggestthatEMTdriversplayregulatoryfunctionsincelldifferentiat...
