Beyondtranscriptionfactors:howoncogenicsignalingreshapestheepigeneticlandscapeFanLiu1,2,LanWang5,6,FabianaPerna3,andStephenD.Nimer1,2,4,*1DepartmentofBiochemistryandMolecularBiology,UniversityofMiami,MillerSchoolofMedicine,Miami,FL331362SylvesterComprehensiveCancerCenter,UniversityofMiami,MillerSchoolofMedicine,Miami,FL331363MolecularPharmacologyandChemistryProgram,Sloan-KetteringInstitute,MemorialSloan-KetteringCancerCenter,NewYork,NY100654DepartmentofInternalMedicine,UniversityofMiami,MillerSchoolofMiami,FL331365InstituteofHealthSciences,ShanghaiInstitutesforBiologicalSciences,ChineseAcademyofSciences/SchoolofMedicine,ShanghaiJiaoTongUniversity,Shanghai,China6StateKeyLaboratoryofMedicalGenomics,ShanghaiInstituteofHematology,RuiJinHospital,SchoolofMedicine,ShanghaiJiaoTongUniversity,Shanghai,ChinaAbstractCancer,oncethoughttobecausedlargelybygeneticalterations,isnowconsideredtobeamixedgeneticandepigeneticdisease.Theepigeneticlandscape,whichisdictatedbycovalentDNAandhistonemodifications,isprofoundlyalteredintransformedcells.Theseabnormalitiesmayariseduetomutationsinoralteredexpressionofchromatinmodifiers.Recentreportsontheinterplaybetweencellularsignalingpathwaysandchromatinmodificationsaddanotherlayerofcomplexitytothealreadycomplexregulationoftheepigenome.InthisReview,wediscussthesenewstudiesandhowtheinsightstheyprovidecancontributetoabetterunderstandingofthemolecularpathogenesisofneoplasia.Signaltransductionpathwaysconvertenvironmentalstimulitochangesincellbehavior,andarethuscentraltothecontrolofallbiologicalprocesses.Notsurprisingly,deregulationofthesepathwayscontributestothedevelopmentofmanydiseases,andisparticularlyimportantinthecontextofcancer.Extensivestudiesoverthepastdecadeshaveidentifiedgeneticalterationsincomponentsofmanysignalingpathwaysinvolvedincancer,andhavealsoledtothedevelopmentoftherapeuticsthatcansuccessfullytargetsomeofthesepathways,mostnotablytheuseoftyrosinekinaseinhibitorsinchronicmyeloidleukemia1,HER2(alsoknownasERBB2)inhibitorsinbreastcanc...
