癌细胞中葡萄糖代谢与转运特点

2014203JournalofChineseOncology,2014,Vol.20,No.3，，(，，510060)：，Na+1（SGLT1），，SGLT1。，SGLT1，，，。：SGLT1；；：R730：A：1671-170X（2014）03-0244-04doi：10.11735/j.issn.1671-170X.2014.03.B016TheCharacteristicsofGlucoseMetabolismandTransportinCancerCellsCHENPing，XIALiang-ping，ZHANGPei（SunYatsenUniversityCancerCenter，Guangzhou510060，China）Abstract：Malignanttumorconsumeslargeamountsofglucosethroughhighlyreactiveglycoly-sis，inwhichprocesssodium-dependentglucosetransporter(SGLT1)isanimportanttransportmodeforcancercellstogetalargenumberofglucose，aswellasmaintainstheirsurvival.Com-pletelyblockingofSGLT1mayinduceautophagicprogrammedcelldeathoftumorcells.Therefore，SGLT1iscloselyrelatedtotheglucosemetabolismandtransportincancercells，andsotothecarcinogenesisanddevelopmentofmalignanttumors，italsoshowsaclinicalsignifi-cancetotheevaluationoftreatmenteffectandprognosis.Forthesereasons，SGLT1mightbeanewtargetformalignanttumorstherapy.Subjectwords：sodium-dependentglucosetransporter(SGLT1);cancercells;glucosemetabolism：（81272641，81071872）：，，，；，651（510060）；E-mail：[e-mail]：2013-08-26；：2013-10-0711．1，，ATP［1］。PET-CT：18F-FDG，，［2］。1．2，，1920OttoWarburg，“WarburgEffect”（Warburg），，ATP，Warburg［3，4］，。，。，，ATP，，，［5］。，，、2442014203，，，，［6］。1.3M2M2(pyruvatekinaseM2，PKM2)。M（PKM）PKM1PKM2，PKM1，PKM2，［7］。，PKM2，PKM1，PKM2，。PKM2，PKM2［8］。PKM2，，。PKM2PKM1，War-burg，，［9］。，PKM2，，，，ATP，PKM2，PKM2（gatekeeper），［10］。PKM2［11］，，D1［12］、OCT-4［13］、Myc［14］、mTOR［15］、MUC1-C［16］。，PKM2HIF-1，HIF-1PKM2，PKM2HIF-1，PKM2，PKM2［17，18］。，PKM2，。PKM2［19］。2：—（Na+-glucosecotransporter，SGLTs），Na+，Na+/K-ATP，。（facili-tatealglucosetransporters，GLUTs），，，，［20］。SGLTs，GLUTs。2.1SGLT1SGLTSGLT1SGLT2，SGLT1Na+—，，SGLT2，。SGLT1，SGLT122q11，2→qter，664，D-D-，［21］。SGLT1，EGFR，0.89，EGFRSGLT1［22］。，，SGLT1。［23］SGLT1，、、、Na+pH，SGLT1，SGLT1mRNA，Na+SGLT1，SGLT1pH。Alesutan［24］SGLT1TTBK2———/，，。Leiprecht［25］HPV18E6SGLT1，SGLT1，SGLT1。Castaneda-Sceppa［26］SGLT1。2.2GLUT1GLUT1GLUTs，。，GULT1，。GULT1，2452014203JournalofChineseOncology,2014,Vol.20,No.3［27］。3SGLT1、SGLT1，39.7%，11.5%，10%，SGLT1。，，SGLT1，SGLT1、［28］。SGLT1，，，SGLT1［29］。，SGLT1MAP17ROS，50%SGLT1，，SGLT1、。，MAP17SGLT1，MAP17SGLT1，，［30］。，SGLT1EGFR，，SGLT1（overallresponserate，ORR）［31］。，SGLT1EGFR，，［22］。Casneuf［32］，，SGLT1（disease-freesurvival，DFS）、（overallsurvival，OS），（63.9），SGLT1。，SGLT1，，SGLT1，［33］。4SGLT1（autophagy），，、，。，，。，，，，，，［34，35］。SGLT1。SGLT1EGFR，EGFR［23，27］。EGFR，EGFR，SGLT1。，SGLT1，，50%，，。，SGLT1EGFR［27］。5SGLT1，。SGLT1PKM2、，SGLT1，。EGFR，SGLT1，EGFR，；，EGFRSGLT1。：[1］NishimuraY，RomerLH，LemastersJJ.Mitochondrialdys-functionandcytoskeletaldisruptionduringchemicalhy-poxiatoculturedrathepaticsinusoidalendothelialcells：thepHparadoxandcytoprotectionbyglucose，acidoticpH，andglycine[J].Hepatology，1998，27(4)：1039-1049.[2]JohannesC，MichaelE.Positronemissiontomographyscanning：currentandfutureapplications[J].AnnuRev2462014203Med，2002，53：89-112.[3]DeBerardinisRJ.Iscanceradiseaseofabnormalcellularmetabolism？Newanglesonanoldidea[J].GenetMed，2008，10(11)：767-77.[4]MatthewG.VanderH，LewisC，etal.UnderstandingtheWarburgeffect：themetabolicrequirementsofcellprolif-eration[J].Science，2009，324(5930)：1029-33.[5]DimitriosA，GeorgeP，LewisC.Cantley，etal.InhibitionofpyruvatekinaseM2byreactiveoxygenspeciescon-tributestocellularantioxidantresponses[J].Science，2011，334(6060)：1278-1283.[6]GilliesRJ，RobeyI，GatenbyRA.Causesandconse-quencesofincreasedglucosemetabolismofcancers[J].JNuclMed，2008，49(Suppl2)：24S-42S.[7]HarrisI，McCrackenS，MakTW.PKM2：agatekeeperbe-tweengrowthandsurvival[J].CellRes，2012，22(3)：447-449.[8]ChristofkHR，VanderHeidenMG，HarrisMH，etal.TheM2spliceisoformofpyruvatekinaseisimportantforcancermetabolismandtumourgrowth[J].Nature，2008，452(7184)：230-233.[9]Mazurek，S.PyruvatekinasetypeM2：akeyregulatorofthemetabolicbudgetsystemintumorcells[J].IntJBiochemCellBiol，2011，43(7)：969-980.[10]GuptaV，BamezaiRN.HumanpyruvatekinaseM2：amulti-functionalprotein[J].ProteinSci，2010，19(11)：2031-2044.[11]LuZ.NonmetabolicfunctionsofpyruvatekinaseisoformM2incontrollingcellcycleprogressionandtumorigenesis[J].ChinJCancer，2012，31(1)：5-7.[12]YangW，XiaY，JiH，etal.NuclearPKM2regulatesbeta-catenintransactivationuponEGFRactivation[J].Nature，2011，480(7375)：118-122.[13]LeeJ，KimHK，HanYM，etal.PyruvatekinaseisozymetypeM2(PKM2)interactsandcooperateswithOct-4inregulatingtranscription[J].IntJBiochemCellBiol，2008，40(5)：1043-1054.[14]DavidCJ，ChenM，AssanahM.HnRNPproteinscon-trolledbyc-MycderegulatepyruvatekinasemRNAsplic-ingincancer[J].Nature，2010，463(7279)：364-368.[15]SunQ，ChenX，MaJ，etal.Mammaliantargetofra-pamycinup-regulationofpyruvatekinaseisoenzymetypeM2iscriticalforaerobicglycolysisandtumorgrowth[J].ProcNatlAcadSciUSA，2011，108(10)：4129-4134.[16]KosugiM，AhmadR，AlamM，etal.MUC1-ConcoproteinregulatesglycolysisandpyruvatekinaseM2activityincancercells[J].PLoSOne，2011，6(11)：e28234.[17]LuoW，HuH，ChangR，etal.PyruvatekinaseM2isaPHD3-stimulatedcoactivatorforhypoxia-induciblefactor1[J].Cell，2011，145(5)：732-744.[18]LvL，LiD，ZhaoD，etal.AcetylationtargetstheM2iso-formofpyruvatekinasefordegradationthroughchaper-one-mediatedautophagyandpromotestumorgrowth[J].MolCell，2011，