Metabolicreprogrammingandepithelial-to-mesenchymaltransitionincancerMarcoSciacovelliandChristianFrezza*MedicalResearchCouncilCancerUnit,UniversityofCambridge,Hutchison/MRCResearchCentre,Box197,CambridgeBiomedicalCampus,Cambridge,UnitedKingdom,CB20XZAbstractSeverallinesofevidenceindicatethatduringtransformationepithelialcancercellscanacquiremesenchymalfeaturesviaaprocesscalledepithelial-to-mesenchymaltransition(EMT).Thisprocessendowscancercellswithincreasedinvasiveandmigratorycapacity,enablingtumourdisseminationandmetastasis.EMTisassociatedwithacomplexmetabolicreprogramming,orchestratedbyEMTtranscriptionfactors,whichsupporttheenergyrequirementsofincreasedmotilityandgrowthinharshenvironmentalconditions.ThediscoverythatmutationsinmetabolicgenessuchasFH,SDHandIDHactivateEMTprovidedfurtherevidencethatEMTandmetabolismareintertwined.Inthisreview,wediscusstheroleofEMTincancerandtheunderpinningmetabolicreprogramming.Wealsoputforwardthehypothesisthat,byalteringchromatinstructureandfunction,metabolicpathwaysengagedbyEMTarenecessaryforitsfullactivation.BackgroundInthelastdecades,cancerresearchuncoveredthemanyenablingfeaturesoftumourscells[1].Amongthese,activationofepithelial-to-mesenchymaltransition(EMT),aprocesswhereepithelialcancercellsacquiremesenchymalfeatures,isemergingaskeydeterminantofcancercellinvasionandmetastasis[2–4].Tometastasise,cancercellsacquiretheabilitytoerodetheextracellularmatrix,themotilitytoextravasateintothebloodstream,andtheplasticitytogrowinadifferenttissue.Inallthesephases,nutrientsupplycanbelimitedandcancercellsexperiencevaryingdegreeofstress[5].Accordingly,metastaticcellsfine-tunetheirmetabolismtoadapttotheever-changingenvironment[6,7].Inlinewiththisobservation,partofthegeneticreprogrammingorchestratedbyEMTaffectstheexpressionofmetabolicgenes,regulatingglucose,lipids,glutamine,andnucleotidemetabolism.Yet,towhatextentEMTrewiresthemetabolicnetworkisstillunclear.Therecentdiscoverythat*towhomcorrespondenceshouldbeaddressed:cf366@MRC-CU.cam.ac.uk.Compe...
