REVIEWRolesandepigeneticregulationofepithelial–mesenchymaltransitionanditstranscriptionfactorsincancerinitiationandprogressionJeong-YeonLee1•GuKong2Received:29April2016/Revised:15July2016/Accepted:19July2016�SpringerInternationalPublishing2016AbstractTheepithelial–mesenchymaltransition(EMT)isacrucialdevelopmentalprocessbywhichepithelialcellsundergoamesenchymalphenotypicchange.DuringEMT,epigeneticmechanismsincludingDNAmethylationandhistonemodificationsareinvolvedintheregulationofEMT-relatedgenes.TheepigeneticgenesilencingoftheepithelialmarkerE-cadherinhasbeenwellcharacterized.Inparticular,threemajortranscriptionalrepressorsofE-cadherin,Snail,ZEB,andTwistfamilies,alsoknownasEMT-inducingtranscriptionfactors(EMT-TFs),playacrucialroleinthisprocessbycooperatingwithmultipleepigeneticmodifiers.Furthermore,recentstudieshaveidentifiedthenovelepigeneticmodifiersthatcontroltheexpressionofEMT-TFs,andthesemodifiershaveemergedascriticalregulatorsofcancerdevelopmentandasnoveltherapeutictargetsforhumancancer.Inthisreview,thediversefunctionsofEMT-TFsincancerprogression,thecooperativemechanismsofEMT-TFswithepigeneticmodifiers,andepigeneticregulatoryrolesfortheexpres-sionofEMT-TFswillbediscussed.KeywordsEMT�EMTtranscriptionfactor�Humancancer�Epigenetics�Chromatin�Histonemodification�DNAmethylationIntroductionTheepithelial–mesenchymaltransition(EMT)isaprocesswherebyepithelialcellslosetheirepithelialcharacteristics,suchaspolarityandcell–celladhesion,andadoptmes-enchymalphenotypeswithmotileandmigratoryabilities.Duetothesefeatures,EMTplaysdiverserolesinaseriesofdevelopmentalandphysiologicalprocessesincludingembryogenesis,tissuehomeostasis,woundhealing,andstemcellplasticity[1,2].Incancerdevelopment,EMThasbeenregardedasaninitialstepfortumormetastasisbecauseEMTinducestumorcelldisseminationandsub-sequentlyincreasescellmigrationandinvasion[3,4].Furthermore,EMThasbeeninvolvednotonlyintumorinvasionandmetastasisbutalsointumorgrowthandangiogenesisandthegenerationofcancerstem-likecell...
