WntVOǐՂƂVK̍R܂̊J

<strong>{^iEer </strong>
iww@wn qaԐwj
emailF<a href="mailto:shinjim@molbiobc.med.osaka-u.ac.jp">{^i</a>C<a href="mailto:akikuchi@molbiobc.med.osaka-u.ac.jp">er </a>
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̈Zr[, <strong>7</strong>, e009 (2018)@<a href="http://dx.doi.org/10.7875/leading.author.7.e009">DOI: 10.7875/leading.author.7.e009</a>
Shinji Matsumoto & Akira Kikuchi: <strong>Wnt signaling pathways in cancers: key targets and implications in cancer therapy.</strong>

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<h2>v </h2>
@Wnt͕含^pNłCWntVOi`BoH邱ƂɂCBCCזE^CɐȂǁCɂ킽זẺ𐧌䂷DWntVOȋِ͓ɂ锭̉ߒɕK{łCX̑̌`𐧌䂷Dô̂ɂ͑̍P퐫̈ێɊ֗^CĐC̉ߒɂĊDC咰͂߂Ƃqg̎X̂ɂāCWntVOi`BoḦُȊ̊֗^ɂĕ񍐂ĂD܂ŁCWntVOi`BoH̎ՒfړIƂR܂̊J݂Ă̂́CiƂĎpꂽ͂ȂDCߔÑqĝQm̖ԗIȉ͂IKmCh|{ZpƂ܂āCVȂVOi^pN̔ѕqWIÖ̊J҂ĂD

<h2>͂߂</h2>
@1982NC}EX̓̌`qƂ<em>Int-1</em>`qN[jOCVEWEoGɂ<em>Int-1</em>`q̃zO<em>Wingless</em>`qƂ߂̌`ɏdvȖ͂`qłƂCInt-1Wnt-1iWingless + Int-1jƖÂꂽ<a href="#R1"><sup>1)</sup></a>Dꂩ35NȏオCᇈwCwCזEwɂĂ͂i݁CWnť̈͑傫WJĂDqĝɂWntVOȉdv́Cɑ咰ɂĖ炩ɂĂDCߔÑqĝQm̖ԗIȉ͂CזĚɂĔWIKmCh|{Zp̉pȂǂɂCWntVOi`BoH̍\^pNWnt֘A^pNُ̈킪qg̑lȂɊ֗^邱Ƃ炩ɂĂDŁC܂ŁCWntVOi`BoH̎ՒfړIƂR܂̊J݂Ă̂́CʂƈS̖肩iƂĎpꂽ͂ȂD̃r[ɂẮC܂łɖ炩ɂĂWntVOi̊̋@\ɊւmCqĝɂWntVOi`BoH̍\^pNُ̈C܂C݁CՏi߂ĂWnt֘A^pNWIɂR܂̊JɂĉD

<h2>1DWntVOi`BoH̊Tv</h2>
@Wnt͕qʂ4̕含^pNŁCVEWEoGMɂ܂ŎĕۑC`Ԍ`C܂Cô̂̑BCCזE^CɐȂǂ𐧌䂷<a href="#R2"><sup>2)</sup></a>DWntVOi`BoHɂ́CJejĈ`q̔𐧌䂷JejoHƁCJejoHƂ͓ƗƂčזEiזE^Ȃǂ𐧌䂷JejˑoH݂<a href="#R3"><sup>3)</sup></a>i<a href="#F1">}1</a>jD܂łɁCKhƂĂWnt̓qgу}EXɂ19ނ肳Ă<a href="#R2"><sup>2)</sup></a>D܂CWnt̎êƂẮC7񖌊ђʌ^FrizzlediFz1`Fz1010ށjɂ킦C1񖌊ђʌ^LRP5CLRP6CRor2CRyk݂<a href="#R3"><sup>3)</sup></a>DȂƂCJejoH̊ɂ1ނFrizzledLRP5邢LRP6êƂċ@\DCWnt5aFrizzledCRor1邢Ror2ƎOҕ̂`邱ƂɂJejˑoH<a href="#R4"><sup>4)</sup></a>D

<a name="F1"></a><div id="fig1-caption-text" style="display: none;"><strong>}1@WntVOi`BoH̑l</strong>
WntVOi̓JejoHCPCPoHCCa<sup>2+</sup>oH3̌oHD
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2018/12/Kikuchi-7.e009-Fig.1.jpg" target="_blank">[Download]</a></div>[hs_figure id=1&amp;image=/wordpress/wp-content/uploads/2018/12/Kikuchi-7.e009-Fig.1.png&amp;caption=fig1-caption-text]

@<strong>Wnt^pN̖|Cƕ</strong>FׂĂWnt͍̉ߒɂďÊɋǍ݂AV]ڍyfPorcnɂp~gCDCWnt́Ĉ̂C7񖌊ђʌ^\[eBOêłEvi/WlsƌCSŴWlsɈˑIɍזEOւƕ傳DWnt̕ɂƂȂזEɈڍsWlśCg}[̂ɂtsAɂSŴɂǂ<a href="#R5"><sup>5)</sup></a>DPorcnɂ鎉CWnt݂̂̕Ȃ炸CêƂ̌aIȍזEƂ̐eaɂ^DقƂǂ̏ꍇCWnt͂̑aɋ߂ɂזEɑ΂pƍlĂ邪C傳ꂽWntWIɂȂזEɂ܂ŗA@\ɂẮCړIȕCGL\\[C|^pNqɂAȂǂĂ̂́C܂RƂȂi<a href="#F2">}2</a>jD

<a name="F2"></a><div id="fig2-caption-text" style="display: none;"><strong>}2@Wnt̕oH</strong>
Wnt́CÊɂPorcnɂp~gCiCjCWlsɈˑIɍזEOւƕ傳D
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2018/12/Kikuchi-7.e009-Fig.2.jpg" target="_blank">[Download]</a></div>[hs_figure id=2&amp;image=/wordpress/wp-content/uploads/2018/12/Kikuchi-7.e009-Fig.2.png&amp;caption=fig2-caption-text]

@<strong>JejoH</strong>FJej̓Jhw^pNƂē肳CזEڒɏdvȂ͂炫ƓɁCWntVOĩfBG[^[ƂĂ@\DWntɂĥȂԂɂẮCזẼJejAxinCAPCCGSK-3ȂAxin̂ɂ郊_ƁCɂƂȂ-TrCPɂ郆rL`CŏIIɂ̓veA\[ɂ蕪邽߁CJej̗ʂ͒Ⴂxɕۂ<a href="#R3"><sup>3)</sup></a>DWnt3aWnt1ȂǂêłFrizzled邢͋êłLRP5CLRP6ƌƁCDvlזEւƃN[g錋ʁCAxin̂̋@\}CJej͈艻ĊjւƈڍŝC]ʈqłTcf/LefƌC<em>Cyclin D1</em>`qc-<em>Myc</em>`qȂǂ̔𑣐i邱ƂɂזȆB╪𐧌䂷D
@<strong>JejˑoH</strong>FJejˑoHɂ́CʓזEɐiplanar cell polarityFPCPj𐧌䂷PCPoHƁCזEɂCa<sup>2+</sup>̓𑣐iCa<sup>2+</sup>oH́CȂƂ2ނ݂<a href="#R3"><sup>3)</sup></a>DWnt5aWnt11ȂǂêłFrizzled邢͋êłRor1CRor2CRykƌƁCזEɂđlȃJejˑoHD1̌oHłPCPoH́CVEWEoG̕\ʂɂ1w̏זE`т̔z肷VOi`BoHƂČoꂽDPCPoHFrizzled邢DvlRhot@~[̒ᕪqG^pNCɁCRhoLi[[JNK̊ɂזEi𐧌䂵čזEɐזE^C܂C`q̔𑣐iD2̌oHłCa<sup>2+</sup>oHɂẮCWntזEɂCa<sup>2+</sup>̓ЂNCCaMKPKC邱Ƃ񍐂ĂDIȈӋ`͕sł邪CJejˑoH̓JejoHɑ΂hR邱ƂĂ<a href="#R6"><sup>6)</sup></a>D̂悤ɁCPCPoHCa<sup>2+</sup>oĤقɂJejȂVOi`BoH݂̑oĂCJejˑoH͑lƍl<a href="#R7"><sup>7)</sup></a>D
@<strong>R-spondinoH</strong>Fŋ߂ɂȂCWntWntêɂ킦CJejoH͂ɑ3̃^pNƂR-spondiniRspo1`Rspo44ށj肳CqĝƂ̂񍐂ĂDR-spondin̎ĥȂԂɂẮCђʌ^̃rL`K[[łRNF43/ZNRF3͍זEFrizzledrL`CFrizzled̓\\[ɂĕDR-spondinזEɂLGR4CLGR5CLGR6RNF43/ZNRF3ƌƁCRNF43/ZNRF3ȃrL`ɂזE珜ČʁCFrizzledזEɂĈ艻JejoH𑝋<a href="#R8"><sup>8)</sup></a>i<a href="#F3">}3</a>jDR-spondinVOiFrizzled̈艻ЂNƂCJejoHɂ킦JejˑoHƍlĂ邪C̐IȈӋ`ɂĂ͏\ɉ𖾂ĂȂD

<a name="F3"></a><div id="fig3-caption-text" style="display: none;"><strong>}3@R-spondin-RNF43/ZNRF3VOiɂJejoH̐@\</strong>
iajR-spondinȂD
ibjR-spondinD
RNF43/ZNRF3Frizzled̃rL`ƕЂNCJejoH}DR-spondinRNF43/ZNRF3LGR4CLGR5CLGR6ƌƁCRNF43/ZNRF3͍זE珜CFrizzled艻邱ƂɂJejoHD
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2018/12/Kikuchi-7.e009-Fig.3.jpg" target="_blank">[Download]</a></div>[hs_figure id=3&amp;image=/wordpress/wp-content/uploads/2018/12/Kikuchi-7.e009-Fig.3.png&amp;caption=fig3-caption-text]

@̂悤ɁCWnt͕̍זEVOi`B@\邱ƂɂCʂȍזE𐧌䂷DāCWntVOi`BoHɈُ킪ƁC͂߂ƂĎX̎ЂN<a href="#R9"><sup>9)</sup></a>D

<h2>2DJejoḦُƂ</h2>
@ߔNCgDזE<em>in vitro</em>ɂĔ|{IKmCh|{Zp}ɔWCWntVOiǁC݁C̑XƂ̏gDזȆBшێɏdvȖ͂Ƃ炩ɂC𔭐̕nƂ鑽̂WntVOi֗^\ĂDہCThe Cancer Genome AtlasiTCGAjInternational Cancer Genome ConsortiumiICGCjƂK͂ȂQmvWFNgɂCDNA``q邢̓^pNُ̔̈ɊւԗIȃf[^JCWntVOi`BoH̍\^pNُ̈킪lȂɂĔF߂邱Ƃ炩ɂĂ<a href="#R10"><sup>10)</sup></a>D
@<strong><em>APC</em>`qُ̈</strong>F<em>APC</em>`q͉Ƒ咰Bǂ̌`qƂē肳ꂽ<a href="#R11"><sup>11)</sup></a>DAPC^pN͖2800̃A~m_cȂCAxinуJejƒڂɌăJej̕𑣐iD<em>APC</em>`qُ͉̈Ƒ咰Bǂɂ킦咰ɂĂ80̏ǗŌoĂDƑ咰Bǂ咰ɂ<em>APC</em>`qُ̈̑啔́CrɏI~RhAPCC[̔̂łD̕ψAPC̓JejƂ̌\͕ۂĂ邪CAxinƂ͌łȂDāCJej悭_Ȃ߁CJej̕\ቺ~ςDŋ߂ɂȂCqg̑咰IKmCh̔|{fɂāCCRISPR-Cas9@ɂQmҏWp<em>APC</em>`q܂ޕ̈`qɕψق𓱓邱ƂɂCiK̔<em>in vitro</em>ɂčČCɎۂɑ咰񂪂ЂN邱ƂC̉ߒɂ<em>APC</em>`qُ̈̏dv炽߂ĊmFꂽ<a href="#R12"><sup>12)</sup></a>D
@<strong>Jej`qُ̈</strong>F咰̖15̏ǗŃJej`qُ̈킪F߂C̕ψق̓GL\3ɏWĂ<a href="#R11"><sup>11)</sup></a>D̗̈ɂCK1GSK-3ɂ胊_A~m_zCсC-TrCPɂ郆rL`̔Fz񂪑݂D̃A~m_c̕ψفC邢́CGL\3̊S邢͕ɂCJejCK1GSK-3ɂ胊_ȂȂC邢́CrL`ȂȂCψكJej͍זEjɒ~ςDJej`qُ̈́C̑Ct玿C݂COBĈł̉ȂǂɂčpxŔF߂D
@<strong><em>Axin</em>`qُ̈</strong>Fqgɂ<em>Axin1</em>`q<em>Axin2</em>`qibg<em>Axil</em>`qC}EX<em>conductin</em>`qj2<em>Axin</em>`q݂C̑ɂ<em>Axin1</em>`qC咰ɂ<em>Axin2</em>`qُ̈킪񍐂Ă<a href="#R13"><sup>13,14)</sup></a>DAxinُ̈ɂAPCCJejCGSK-3Ƃ̂̕`ȂȂCJej̃_⃆rL`}ČʁCJej~ςƍlĂD
@<strong>R-spondinoHɂ`qُ̈</strong>Fŋ߂ɂȂC<em>RNF43</em>`q̋@\ψقX<a href="#R15"><sup>15)</sup></a> ё咰<a href="#R16"><sup>16)</sup></a> ɂāC܂C<em>ZNRF3</em>`q̕ψقt玿<a href="#R17"><sup>17)</sup></a> ɂāC͂߂ĕ񍐂ꂽDɁC<em>Rspo2</em>`q邢<em>Rspo3</em>`q̗Z10̑咰ɂĔF߂Ă<a href="#R18"><sup>18)</sup></a>D咰ɂāC<em>RNF43</em>`q̕ψق邢<em>R-spondin</em>`q̗Z<em>APC</em>`q̕ψق͑ݔrIȊ֌Wɂ邱ƂCWntVOi`BoH̊юᇂ̌`Ɋ֗^ƍlDŁC<em>RNF43/ZNRF3</em>`qɕψقX񂨂ё咰Porcn̑jQ܂Ɋ󐫂ƂCזȆBWnt̕ɋˑ邱Ƃ炩ɂꂽ<a href="#R19"><sup>19,20)</sup></a>D

<h2>3DJejˑoḦُƂ</h2>
@<strong>Wnt5â̈p</strong>FX∫F͂߂Ƃqg̑̂ɂāCJejˑoHWnt5a͍זE^Z\𑣐iCᇂ̐iWɊ֗^<a href="#R6"><sup>6)</sup></a>D񏬍זExɂĂ<em>Wnt5a</em>`q̉ߏȔƎᇂ̑BъԎɂ錌ǂ̐VƂ̂ɐ̑ւF߂<a href="#R21"><sup>21)</sup></a>D݂ɂĂC<em>Wnt5a</em>`q͖30̏ǗɂĉߏɔĂCx̍XLX^ɂWnt5az̏ǗႪLӂɑ<a href="#R22"><sup>22)</sup></a>DɁCWnt5az̏p5N͉̐AɔחLӂɒႢD܂C<em>Wnt5a</em>`qĂOB̏Ǘł͕agDwIȈxCp̍Ĕ<a href="#R23"><sup>23)</sup></a>DāCWnt5a͂ɉĂ̈𑣐ipƂĈɂĂ͐ff}[J[\̔wWC邢́CÂ̕WIɂȂ\D
@<strong>Wnt5â̗}p</strong>Fɑ΂CWnt5a̓JejoH}͂炫邱ƂC̗}pƂlĂ<a href="#R6"><sup>6)</sup></a>DƂ΁CbB◑̍זEɂWnt5a͍זȆB}<a href="#R24"><sup>24,25)</sup></a>ĎʂƈvāCWnt5ãwembNAEg}EX𒷊Ԃɂ킽莔炷ƁC24Jȓɖ20̃}EXɂBp邢͖aRǂ<a href="#R26"><sup>26)</sup></a>Dqg̔aɂĂC<em>Wnt5a</em>`q̔}ǗႪF߂D

<h2>4DWntVOi֘A^pNُ̔̈ƐVK̂VOi</h2>
@JejoH𐧌䂷Axin̂̍\^pN̈`qُ̈ƂƂ̊֌W炩ɂꂽƂC܂ŁCJejoH𒼐ڂɑjQR܂̊Ji߂ĂC܂pɂ͂ĂȂDŁCWntVOi`BoHɊ֘An̕WIɂȂ肤VǨoH̒Ti߂Ăi<a href="#F4">}4</a>jD

<a name="F4"></a><div id="fig4-caption-text" style="display: none;"><strong>}4@ɓِ̍VWnt֘A^pNƂVOi</strong>
񉻂̉ߒɂWnt-JejoHEGF-RasVOiIɊƁCWIɂȂ`qƂĒᕪqG^pNR[h<em>Arl4c</em>`qCArl4c͍זE^эזȆBDC̐@\͕sCזEɓٓI<em>DKK1</em>`q<em>CKAP4</em>`qߏɔƁCDKK1͍זEêłCKAP4ƌ邱ƂɂPI3K-AKTVOiזȆB𑣐iD
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2018/12/Kikuchi-7.e009-Fig.4.jpg" target="_blank">[Download]</a></div>[hs_figure id=4&amp;image=/wordpress/wp-content/uploads/2018/12/Kikuchi-7.e009-Fig.4.png&amp;caption=fig4-caption-text]

@<strong>DKK1ɂ邪זȆB\̑i̕q@\</strong>FDKK1́CLRP6ƌJejoHjQ镪含^pNŁC̔ɕK{ł<a href="#R27"><sup>27)</sup></a>Dô̂̑gDɂ锭͂߂ĒႢCgDɂēٓIȍF߂D̍p@\CsFRP1sFRP2ƓlɁCDKK1̗͂}\ƍlĂC<em>DKK1</em>`qxHɂč邱ƂCRDKK1R̂xזȆB}邱ƂCDKK1WntVOȋjQƂ͊֌WȂCזȆB𑣐i\Ă<a href="#R28"><sup>28-30)</sup></a>DDKK1^pN̒ŤʁCזE1񖌊ђII^^pNłCKAP4DKK1̐VK̎êł邱ƂDDKK1-CKAP4VOíCPI3KAKT邱ƂɂזȆB𑣐i<a href="#R31"><sup>31)</sup></a>D<em>DKK1</em>`q<em>CKAP4</em>`qXCxBCxG炪CHG炪̖40`60̏ǗɂĂgDɓٓIɔĂC<em>DKK1</em>`q<em>CKAP4</em>`qĂǗ́C<em>DKK1</em>`q<em>CKAP4</em>`qƂɔĂȂǗCсCꂩ݂̂ĂǗɔׁC\オLӂɕsǂł<a href="#R31"><sup>31,32)</sup></a>D킦āCDKK1Ɠlɂ̑iʂF߂Ȃ炱܂ŎêsłDKK3CH̖50̏Ǘɂp53t@~[̓]ʈqłp63iTP63jɈˑIɉߏɔCCKAP4čזȆBюᇂ̌`𑣐i邱Ƃ炩ɂĂ<a href="#R33"><sup>33)</sup></a>DɁCRCKAP4R̂C<em>DKK1</em>`q邢<em>DKK3</em>`q𔭌XזECxזECHזE<em>in vivo</em>ɂᇂ̌`}邱ƂCCKAP4͂̂ɂĐVK̐ff}[J[⎡Â̕WIɂȂƍlD
@<strong>Arl4cɂ邪זẺ^ёB\̑i̕q@\</strong>Fqg̑̂ɂăhCo[VOiƂċ@\EGF-RasVOiWnt-JejVOi̋ʂ̕WI`qƂāC<em>Arl4c</em>`q肳ꂽ<a href="#R34"><sup>34)</sup></a>DȏזEɂǏ\̌`̉ߒ́CזE^\ёB\lĊԎւƐNĂߒƗގĂDWnt-JejVOiEGF-RasVOiIɊ<em>Arl4c</em>`qCזĚ`ԕωƊȑBĊǏ\̌`ЂNDArl4c͕ʎ̒ᕪqG^pNłArf6CRacCRho̊𐧌䂵ČʁCYAP/YAZjւƈڍs邱ƂɂזȆB𑣐i<a href="#R34"><sup>34)</sup></a>D܂C<em>Arl4c</em>`q͑咰CxBCxG炪CG炪̖50`80̏ǗɂĎᇕɓٓIɍĂCזẺ^\CZ\CB\𑣐i<a href="#R35"><sup>35,36)</sup></a>D킦āCŋ߂ł́C<em>Arl4c</em>`q݂̔̕d𑣐i邱Ƃ񍐂Ă<a href="#R37"><sup>37)</sup></a>D<em>Arl4c</em>`q͑咰זECxזEĈזEC݂זEɂāCWnt-JejVOi邢EGF-RasVOiɈˑĉߏɔD咰זÊזE<em>in vivo</em>ɂᇂ̌`́CArl4cɑ΂siRNAA`ZXj_̓^ɂ}邱ƂCVWnt֘A^pNƂĎÂ̕WIɂȂ\<a href="#R38"><sup>38)</sup></a>D

<h2>5DWntVOi`BoHWIɂR܂̊J</h2>
@APCJejƂAxin̂̍\^pN̈`qψق̕px̍CWntVOiWIɂ̑jQ܂̊J́CɃJej-TCF̂WIɂĐ͓Iɐi߂ĂDʂɁCj]ʈqɑ΂jQ܂̊J͂ނƂĂāCJej-TCF̂ɑ΂ĂC܂Âɗp悤Ȗ܂݂͑ȂDŁCߔNCWnt̕oHڍׂɖ炩ɂꂽƂŁCWntWntễxł̑jQ܂̊Ji߂ĂDȉC݁CՏsĂvWntVOijQ܂ɂĉi<a href="#F5">}5</a>jD

<a name="F5"></a><div id="fig5-caption-text" style="display: none;"><strong>}5@ՏsĂWntVOiWIɂR</strong>
jQ܂̑Wnt֘AKh邢Wnt֘AêWIɂD̑jQ܂C݁C1邢͑2̗ՏsĂD
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2018/12/Kikuchi-7.e009-Fig.5.jpg" target="_blank">[Download]</a></div>[hs_figure id=5&amp;image=/wordpress/wp-content/uploads/2018/12/Kikuchi-7.e009-Fig.5.png&amp;caption=fig5-caption-text]

@<strong>Porcn邢Wnt̕jQ</strong>Fɏqׂ悤ɁCWnt̍זEOւ̕Porcnɂ鎉CɈˑ邱Ƃ炩ɂCPorcn̑jQ܂̊JiłD܂ŁCIWP-2CWNT-C59CLGK974iWNT974jCETC-159iETC-1922159jJC<em>RNF43</em>`qɕψقX<a href="#R39"><sup>39)</sup></a>C<em>RNF43</em>`q邢<em>R-spondin</em>`q̗Z咰<a href="#R40"><sup>40)</sup></a> ɑ΂RᇌʂmFĂD̂CLGK974ETC-159͓̑咰ɑ΂1̗ՏsĂD
@<strong>זEOWnt֘AKh邢Wnt֘Aêɑ΂jQ</strong>FߔNCWnt֘AKhWnt֘Aêُ̈Ƃ̊֘A񍐂C̑jQ܂JĂD
@OMP-54F28Fz8̃VXeCb`hCƃqgƉuOuGFc̈Ƃ̗Z^pNłCWntɑ΂fRCêƂċ@\JejoHjQ<a href="#R41"><sup>41)</sup></a>DOMP-54F28̓qg̊̂񂨂ї̃}EXւَ̈ڐAɂᇂ̌`}邱ƂmFĂC݁C̉wÖ@Ƃ̕pɂ̂CCXɑ΂1̗ՏsĂD
@OMP-131R10Rspo3ɑ΂郂mN[iR̂ŁC<em>Rspo3</em>`q̗Z咰C邢́C<em>Rspo3</em>`qߏɔ񏬍זEẍَڐAɂᇂ̌`}D݁C]ڐ̑咰ɑ΂đ1̗ՏsĂD
@OMP-18R5Fz7ɑ΂郂mN[iR̂Ƃč쐻ꂽC킦āCFz1CFz2CFz5CFz8ɑ΂F\CJejoHjQ邱ƂɂX̃qĝזËَڐAɂᇂ̌`}<a href="#R42"><sup>42)</sup></a>D݁CXC]ڐC񏬍זExɑ΂1̗ՏsĂD
@OTSA101͕ːʌfɂWFz10ɑ΂郂mN[iR̂ŁCFz10ɂēٓIɉߏɔ邱ƂC݁Cɑ΂1̗ՏsĂ<a href="#R43"><sup>43)</sup></a>D
@<strong>Jej܂ޕ̂ɑ΂jQ</strong>FPRI-724̓JejƓ]ʋqłCBPƂ̌jQᕪqŁCJejɈˑIȈ`q̔jQ<a href="#R44"><sup>44)</sup></a>D݁CJej܂ޕ̂ɑ΂jQ܂ƂĂ͗BC}aCaC咰CXɑ΂1ё2̗ՏsĂD
@<strong>JejˑoHWIɂR</strong>FCirmtuzumabiUC-961jRor1ɑ΂郂mN[iR̂ŁCWnt5a-Ror1VOi`BoHjQ邱ƂɂC<em>Ror1</em>`qߏɔ閝paזȆB}<a href="#R45"><sup>45,46)</sup></a>D݁Cpaɑ΂1̗ՏsĂDFoxy5Wnt5a̗ގyv`hŁCWnt5aVOĩASjXgƂčpDɏqׂ悤ɁCWnt5a͂̂ɂė}Iɍp邪CہC}EXfɂFoxy5͓זE̔xъ̓]ڂ}<a href="#R47"><sup>47)</sup></a>D܂C<em>Wnt5a</em>`q̒ᔭ͓C咰COBɂė\sǂƑւ邱Ƃ<a href="#R48"><sup>48-50)</sup></a>C݁Ĉɑ΂đ1̗ՏsĂDCWnt5a̓JejˑoHĂɑiIɍp邱Ƃ̂ŁCł́CWnt5ãASjXgRᇌʂ𔭊邪̖mȎʂ͍łD݁Cʂ邽߂̃}[J[`q̒T݂Ă<a href="#R51"><sup>51)</sup></a>D

<h2></h2>
@35NȏɂWnť̌ʁCWntVOi`BoḦُ킪qg̑lȂɊ֗^邱Ƃ炩ɂĂDCWntVOiѕ⒰ǂ͂߂Ƃ鑽̐ȑgDזËێCBCɂ߂ďdvȖƂCWntVOiWIɂjQ܂ɂ͂˂ɐ[ȕpOD̂߁CvWntVOi`BoH̍\^pNɂ킦CɓٓIɋ@\VWnt֘A^pNVOi`BoH𓯒肷鎎݂́CC܂܂dvɂȂƍlD܂C̕qWIRᇖƑgݍ킹WntVOijQ鎎݂Cp̉ɂȂ邩ȂD
@ŋ߂ɂȂCWntVOi͂זÊ̂ɂ킦C͂̂ɑ΂ĂlȂ͂炫ƂĂDƂɁCᇖƉuɑ΂ṕCC܂܂ڂ邾낤DہCWnt-JejVOi̊ᇂɂCD8zTזE̔rɂ͂炭ȂǁCRᇖƉu}\Ă<a href="#R52"><sup>52)</sup></a>CWntVOi`BoH̑jQ܂ƂƉuÖ@Ƃ̕pɂ鎡Ìʂ̉P҂D

<h2> </h2>
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</ol>
<div class="au-profile">
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<span class="author">{ ^iiShinji Matsumotoj</span>
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URLF<a href="http://www.med.osaka-u.ac.jp/pub/molbiobc/" target="_blank">http://www.med.osaka-u.ac.jp/pub/molbiobc/</a>
</div>
? 2018 {^iEer  Licensed under <a href="http://creativecommons.org/licenses/by/2.1/jp/" target="_blank">CC \ 2.1 {</a>
