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A Long and Winding Road丗儚乕儖僽儖僌攷巑偲偑傫嵶朎偲撧椙彈巕戝妛

[ 儕儕乕僗丗 2020.02 ]
撧椙彈巕戝妛棟妛晹 壔妛惗柦娐嫬妛壢 惗暔壢妛僐乕僗丂搉绮棙梇

丂尋媶幰偺妝偟傒偺堦偮偵偼丄嫟摨尋媶傪捠偠偰杮妛埲奜偺尋媶幰偲偍屳偄偺摼堄媄傪惗偐偡偙偲偱扨撈偱偼側偐側偐庤偑撏偐側偄崅傒偵庤偑撏偒丄帪偵帺暘偱傕姶怱偡傞傛偆側惉壥傪摼傜傟傞偲偄偆偙偲偑偁傞丅偲偼尵偊崙撪偼尵偆偵媦偽偢崙奜偲偺尋媶偱傕墦嫍棧偱偺嫟摨尋媶偼嬯楯偑懡偄丅嵟嬤偺惗暔妛尋媶偼姰惉傑偱偵帪娫傕偐偐傝丄側偐側偐戝曄偱偡丅岾偄偵傕杮妛偱偦偺傛偆側宱尡傪偟偰丄12擭偐偐傝傑偟偨偑柺敀偄尋媶惉壥傪岞昞偱偒偨偺偱崱夞偛徯夘偄偨偟傑偡丅
丂偑傫偺寬恌偱PET偲尵偆尵梩傪暦偄偨偙偲偑偁傞偐傕偟傟傑偣傫丅偙傟偼丄乽偑傫嵶朎偑僽僪僂摐/僌儖僐乕僗傪懡検偵庢傝崬傓乿偲偄偆摿惈傪棙梡偟偰丄栚偵尒偊側偄偑傫嵶朎偺夠乮庮釃乯傪尒偮偗傞専嵏朄偱偡乮恾1乯丅

恾侾丏儚乕儖僽儖僌岠壥偲PET専嵏偺愢柧
偑傫嵶朎偼惓忢嵶朎偺壗攞傕偺検偺僌儖僐乕僗傪庢傝崬傓偺偱丄僌儖僐乕僗偲摨偠嫇摦傪庢傞18F-FDG乮曻幩惈暔幙乯傪拲幩偡傞偲偑傫偺昦憙偵廤傑傝傑偡丅廤傑偭偨偲偙傠偐傜偼曻幩慄偑曻弌偝傟傞偺偱丄偦傟傪曔傜偊偰夋憸壔偟偰偑傫偺昦憙傪尒偮偗弌偡偙偲偑偱偒傑偡丅乮http://www.hosp.ncgm.go.jp/s037/010/010/pet.html偐傜堷梡乯



丂偙偺乽偑傫嵶朎偑僽僪僂摐乮僌儖僐乕僗乯傪懡検偵庢傝崬傓乿偲偄偆惈幙偼丄100擭傎偳慜偵僲乕儀儖徿庴徿幰偺Otto Warburg偑娤嶡偟偨尰徾偱丄Warburg乮儚乕儖僽儖僌乯岠壥偲屇偽傟傑偡丅偑傫嵶朎偼桳巁慺壓偱傕岠棪偺椙偄儈僩僐儞僪儕傾偺巁壔揑儕儞巁壔傛傝傕丄岠棪偺嬌傔偰埆偄夝摐宯偱惗暔偑僄僱儖僊乕尮偲偟偰巊偆ATP傪嶻惗偡傞偺偱偡丅僌儖僐乕僗偼夝摐宯偱戙幱偝傟偨屻偵儈僩僐儞僪儕傾偵擖傞偙偲側偔僺儖價儞巁僉僫乕僛乮PKM乯偵傛偭偰僺儖價儞巁偵曄姺偝傟丄偑傫嵶朎偼戝検偺僌儖僐乕僗傪徚旓偡傞偙偲偵側傝傑偡乮偙偺曈偼崅峑偺惗暔偺嫵壢彂偵徻偟偔彂偄偰偁傝傑偡乯丅偙傟傜偺ATP嶻惗偺愗傝懼偊偵學傞PKM偱偡偑丄1偮偺堚揱巕偐傜2偮偺惈幙偑堎側傞PKM1偲PKM2偑mRNA偺慖戰揑僗僾儔僀僔儞僌偲偄偆尰徾偵傛偭偰惗傒弌偝傟傞偙偲偑敾柧偟偰偄傑偟偨乮恾2乯丅

恾2. PKM堚揱巕偐傜偼2偮偺僞儞僷僋幙偑偱偒傞

1偮偺堚揱巕偐傜2偮偺惈幙偑堎側傞PKM1偲PKM2偑mRNA偺慖戰揑僗僾儔僀僔儞僌偲偄偆尰徾偵傛偭偰惗傒弌偝傟傞丅恾偱偼丄愒偄巐妏傪巊偊偽PKM1丄椢偺巐妏傪巊偊偽PKM2偲側傞丅PKM2偑儚乕儖僽儖僌岠壥偺尨場偲偝傟傞丅乮惗壔妛 戞91 姫戞1 崋丆pp. 38?43乮2019乯傛傝恾偺堦晹傪堷梡乯



丂嫟摨尋媶幰偺揷徖偝傫乮媨忛偑傫僙儞僞乕尋媶強乯偼丄PKM1偲PKM2偲傪嬫暿偱偒傞峈懱傪嶌惢偟丄偑傫慻怐偱偼PKM2梲惈偺傕偺偑懡偄偙偲偐傜丄偙傟傜椉曽偺婡擻偲敪偑傫偲偺娭楢傪夝愅偟傛偆偲丄14擭慜偵採埬偟偰偒傑偟偨丅巹傕撧椙彈巕戝傊晪擟偟偨偽偐傝偱妛惗傕彮側偔丄斵偺忋巌偺搰偝傫偲怴偟偄偑傫梷惂婡峔偺夝柧傪栚巜偟偰扙儕儞巁壔峺慺PP6偺寚懝儅僂僗嶌惢傪巒傔偰偄傑偟偨丅偙偺偨傔僂乕儅儞僷儚乕晄懌偱傕偁偭偨偺偱偡偑丄捈姶揑偵柺敀偦偆偩偭偨偺偱丄妛惗傪愢摼偟偰嫟摨尋媶傪巒傔傑偟偨丅
丂堚揱巕偺摥偒傪挷傋傞偨傔偵偼堚揱巕偺摥偒傪柍偔偡偙偲偑懡偄偺偱偡偑丄mRNA偺慖戰揑僗僾儔僀僔儞僌偲偄偆尰徾偑偁傞偺偱丄堦曽傪柍偔偟偰傕傕偆堦曽偑摦偔壜擻惈偑偁傝傑偡丅偦偙偱丄傕偲傕偲偁傞PKM1, PKM2偼敪尰偝偣偢偵丄奜偐傜擖傟偨PKM1, PKM2偺偳偪傜偐堦曽偩偗偑敪尰偡傞儅僂僗偺嶌惢傪峴偄傑偟偨丅偲偼尵偊丄彨棃偺娻帯椕傊偺墳梡偺摿嫋傕帇栰偵擖傟偰偄偨偺偱乮嵍偆偪傢寁夋偲屇傫偱偄傑偟偨乯丄岞揑側棟尋偱偺幚尡偑偱偒傑偣傫丅偐偲偄偭偰夛幮偵奜拲偡傞偲1庬椶偵嵟掅偆傫昐枩墌偼巟暐偆偙偲偵側傝丄幚尡傪峴偆愭傪扵偡偺偵嬯楯偟傑偟偨丅寢壥揑偵岎徛傪孞傝曉偟丄嫗戝乮幚旓偱偆傫廫枩墌乯偲儀儞僠儍乕乮僗僥僢僾偺戝敿傪変乆偑峴偆偙偲偱80%僨傿僗僇僂儞僩乯偲慻傫偱儅僂僗傪嶌惢偟傑偟偨丅
丂偦偆偙偆偟偰偄傞偆偪偵Nature偵偑傫嵶朎偺庮釃宍惉偵偼PKM2偑戝帠偲偺嬌傔偰僋儕傾乕側榑暥偑岞昞偝傟崢傪敳偐偟傑偟偨(1)丅偦傟偐傜偼丄PKM堚揱巕攋夡偺榑暥偑弌偰丄mRNA偺慖戰揑僗僾儔僀僔儞僌偺戝屼強丄偼偰偼嶐擭僲乕儀儖徿傪庴徿偟偨掅巁慺墳摎偺戝壠傑偱傕偑帺暘偺場巕偲PKM偲偺娭學偲偄偆宍偱尋媶偵嶲夋偟偰偒傑偟偨丅挊柤側妛弍榑暥偵懡悢偺寢壥偑丄傎傫偲偐偲巚偆榑暥傕偁傝傑偟偨偑丄宖嵹偝傟傑偟偨丅惓捈側偲偙傠丄偙偺傑傑偱偼帪婜傪幐偄帺暘偨偪偺惉壥偼岞昞偱偒側偄偺偱偼側偄偩傠偆偐偲丄嫟摨尋媶幰堦摨愴乆嫲乆偲偟偰偄傑偟偨丅
丂偲偙傠偑埬偢傞偼嶻傓偑傗偡偟偱偡丅儅僂僗偑弌棃忋偑傝偄偞夝愅傪巒傔傞偲丄嬃偄偨偙偲偵敪娻幚尡偱偼PKM2傪敪尰偡傞儅僂僗偱偼偑傫傪敪徢偟傑偣傫偑丄PKM1傪敪尰偡傞儅僂僗偱偼偑傫傪懡悢敪徢偡傞偲偄偆丄Nature偺榑暥偲偼恀媡偺寢壥偲側傝傑偟偨丅嵟弶偼偊偭偲嬃偒傑偟偨偑丄幚尡壢妛幰偵偲偭偰偼偄偐側傞応崌偱傕乭Result is result乭偱偡丅偙傟偵椼傑偝傟偰偦偺屻懡悢偺夝愅傪峴偄傑偟偨丅枮傪帩偟偰Nature偵搳峞偟偨偲偙傠丄嵦戰偺壜斲傪栤偆嵏撉偵夞偭偨偺偱偡偑2偐寧屻偵偁偊側偔宖嵹晄壜偺寢壥偑栠偭偰偒傑偟偨丅壗偲偐岞昞偟側偗傟偽偲偝傜偵1擭娫儊僞儃儘僩乕儉夝愅丄僾儘僥僆乕儉夝愅偲偍嬥偑偐偐傞幚尡傪峴偄丄嵞搙Nature偵搳峞偟偨偲偙傠崱搙偼嵏撉偵傕夞傜偢懍峌偱崒捑丅偟偐偟Cancer Cell偺嵏撉屻丄偨偭傉傝偺捛壛幚尡乮崅妟偺儔僕僆傾僀僜僩乕僾傪巊偭偨戙幱夝愅幚尡乯傪壛偊偰柍帠偵嵦戰偲側偭偨帪偵偼丄嵟弶偺搳峞偐傜2擭嬤偔偑偨偭偰偄傑偟偨丅婐偟偄偲偄偆傛傝偼儂僢偲偟偨偲偄偆偺偑惓捈側婥帩偪偱偟偨丅
丂杮妛偺妛惗2柤偑夝愅偵巊偆2庬椶偺堚揱巕夵曄儅僂僗偺嶌惢傪峴偭偨偙偲丄媨忛偑傫僙儞僞乕尋媶強偺摦暔巤愝偺夵廋岺帠偺偨傔偵丄敪偑傫幚尡偼杮妛偱100旵偺儅僂僗偺宱夁娤嶡傪敿擭娫峴偆乮挷巕偑埆偔側偄偐傪枅擔娤嶡乯側偳丄恖揑偵傕巤愝揑偵傕杮妛偑偐側傝娭梌偟偰偄傞偺偱丄乽榑暥偲偟偰岞昞偱偒偰丄傒傫側杮摉偵傛偐偭偨側偁乿偱偟偨丅偙偙偱巻柺偑恠偒傑偟偨丅徻偟偄尋媶撪梕偼恾3偲榑暥(2)傪嶲徠偟偰偔偩偝偄丅


恾3. 怴偟偔敾柧偟偨PKM1, 2偺僄僱儖僊乕嶻惗偵偍偗傞栶妱

PKM1偼丄僌儖僐乕僗乮Glucose丗愒乯桼棃扽慺偺TCA夞楬傊偺棳擖偲擕巁乮Lac乯傊偺曄姺偺偄偢傟傪傕懀恑偝偣傞乮僌儖僐乕僗徚旓傪槾恑乯丅戙幱僱僢僩儚乕僋偺曄壔偑丄枹夝柧偺惂屼婡峔傪捠偠偰憤擕巁嶻惗傪掅壓偝偣傞丅PKM2偼丄僌儖僞儈儞乮Gln丗椢乯徚旓傪槾恑偝偣丄擕巁嶻惗偑憹壛偡傞乮僌儖僞儈儞徚旓傪槾恑乯丅乮Cancer Cell 33, 355-367.傛傝恾偺堦晹傪堷梡乯

嶲峫暥專

(1) Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, Wei R, Fleming MD, Schreiber SL, Cantley LC. (2008) The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth.
Nature 452, 230-233. doi: 10.1038/nature06734.

(2) Morita M, Sato T, Nomura M, Sakamoto Y, Inoue Y, Tanaka R, Ito S, Kurosawa K, Yamaguchi K, Sugiura Y, Takizaki H, Yamashita Y, Katakura R, Sato I, Okada Y, Watanabe H, Kondoh G, Matsumoto S, Kishimoto A, Obata M, Matsumoto M, Fukuhara T, Motohashi H, Suematsu M, Komatsu M, Nakayama K, Watanabe T, Soga T, Shima H, Maemondo M and Tanuma N. (2018) Pkm1 confers metabolic advantages and promotes cell-autonomous tumor cell growth.
Cancer Cell 33, 355-367. e7. doi: 10.1016/j.ccell.2018.02.004.乮擇廳壓慄偼杮妛強懏幰乯