GlucoseGlucose-6-phosphateFructose-6-phosphateFructose-1,6-bisphosphate3-phosphoglyceratePhosphoenolpyruvateLactateRibose-5-phosphatePKM2PHGDHSerineGlycineGLUTAMINEAcetyl-CoAPyruvateSuccinyl-CoAGlutamateGLDC*OxaloacetateIDH2HKIITHFCH2-THFCO2ACLMalonyl-CoAFattyacidsFASNADHNAD+F2,6-bisPPFKFB3+Acetyl-CoACitrateIsocitrateα-ketoglutarate2-hydroxyglutarateIDH1LDHAPGAM1AspartateOxaloacetateAcetyl-CoARibose-5-phosphateSerineGlycineGLDC*THFCH2-THFGLDC*CO2PROTEINSNUCLEOTIDESGLUCOSELIPIDSGlutamineNADHNAD+IDH1GlutamineAMINOACIDSAminoacidstRNAtRNAMYCmTORNH4+NH4+AktTyr-KGrowthfactorRTKPI3KSuccinyl-CoATCACYCLEFructose-6-phosphateFructose-1,6-bisphosphate3-phosphoglyceratePhosphoenolpyruvateF2,6-bisPPFKFB3+PGAM1NADHNAD+GLYCOLYSISα-ketoglutarateIsocitrateMalateOxaloacetateSuccinateFumarateSDHFHCitratePyruvateGlucoseGlycolysisGlutamineGlutaminolysisTobiomassTobiomassGlucoseTCAcycleGlutamineFattyacidsQuiescentcellProliferatingcellCO2ATPCO2ATPSnapShot:CancerMetabolismPathwaysLydiaW.S.Finley,JiZhang,JiangbinYe,PatrickS.Ward,andCraigB.ThompsonCancerBiologyandGeneticsProgram,MemorialSloan-KetteringCancerCenter,NewYork,NY10065,USASeeonlineversionforlegendandreferences.466CellMet.17-3,March5,2013©2013ElsevierInc.DOIhttp://dx.doi.org/10.1016/j.cmet.2013.02.016enzymeOncogenicalterationfunctionaloutcomePFKFB3ThePFK2isoformPFKFB3ishighlyexpressedinseveralhumancancers,includingcolon,prostate,breast,ovary,andthyroid.MostPFK2isoformsbothgenerateanddegradeF-2,6-bisP,whichactivatesPFK1toincreasefluxthroughglyco-lysis.PFKFB3hasnophosphataseactivityanditskinaseactivitymaybestimulatedbyseveraloncogenicevents,furtherpromotingglycolyticflux.PHGDHGenomicregionscontainingthePHGDHgeneareamplifiedinbreastcancerandmelanoma.PHGDHoverexpressionnotonlyincreasesserinesyntheticpathwayfluxtosustaincellproliferationbutalsogeneratesαKG.PGAM1PGAM1isupregulatedincolorectalcancerandhepatocellularcarcinoma,likelyduetoTP53loss.PGAM1balancesintracellular3-phosphoglycerateand2-phosphoglyceratelevels,whichregulateoxid...
