REVIEWARTICLEOPENTheinteractionbetweenferroptosisandlipidmetabolismincancerDingshanLi1andYongshengLi1,2Ferroptosisisanewformofprogrammedcelldeathcharacterizedbytheaccumulationofiron-dependentlethallipidperoxides.Recentdiscoverieshavefocusedonalterationsthatoccurinlipidmetabolismduringferroptosisandhaveprovidedintriguinginsightsintotheinterplaybetweenferroptosisandlipidmetabolismincancer.Theirinteractionregulatestheinitiation,development,metastasis,therapyresistanceofcancer,aswellasthetumorimmunity,whichoffersseveralpotentialstrategiesforcancertreatment.Thisreviewisabriefoverviewofthefeaturescharacterizingtheinteractionbetweenferroptosisandlipidmetabolism,andhighlightsthesignificanceofthisinteractionincancer.SignalTransductionandTargetedTherapy(2020)5:108;https://doi.org/10.1038/s41392-020-00216-5INTRODUCTIONDeathistheinevitablefateoflife.Todate,severaltypesofcelldeath,includingapoptosis,autophagy,necroptosis,pyroptosis,andferroptosishavebeendescribed.1–4Ferroptosis,auniqueformofprogrammedcelldeath,ischaracterizedbytheaccumulationofiron-dependentlethallipidperoxides(LPO).4Itiswellknownthatlipidmetabolismplaysanextremelyimportantroleinvarioustumorproperties,includingtumorigenesis,invasion,andmetas-tasis.5Forexample,highsaturationlevelsofmembranelipidsprotectcancercellsfromdamageinducedbyreactiveoxygenspecies(ROS),sincesaturatedmembranelipidsarelesssensitivetoperoxidation.6,7Moreimportantly,ferroptosisisdrivenbylipidperoxidation,4andLPOarealsoinvolvedincellsignalingeventsasintermediatesforthesynthesisofeicosanoids,8whichregulatecellproliferation,survival,invasion,andmigration.9Inaddition,thearachidonoyl(AA)andadrenoyl(AdA)phospholipidscanbeoxidizedtoproduceLPObythecatalysisofacyl-CoAsynthetaselong-chainfamilymember4(ACSL4)and15-lipoxygenase(15-LOX/ALOX15).10,11Therefore,theregulationoflipidmetabolismandferroptosisoffersseveralpotentialstrategiesfortreatingcancer.Inthisreview,wewilldiscusstheinteractionbetweenferroptosisandlipidmetabolismincancer.FEATURESOFFERROPTOS...
