pp. Wnt Wnt Wnt Wnt β- PCP Ca Wnt Wnt Wnt Wnt Wnt Wingless Wg int- Wingless int Wnt Wnt Wnt β- β- planar cell polarity PCP PCP Ca Ca Wnt β- β- Wnt Wnt signaling; its abnormalities and diseases Akira Kikuchi Department of Biochemistry, School of Biomedical Sciences, Hiroshima University,, Kasumi, Minami-ku, Hiroshima, Japan β- Wnt β- β- PCP PCP Wnt Frizzled Fz Dishevelled DvlRho G GTP Rho Rho kinase Jun Jun-Nterminal kinase JNK Ca Wnt Ca Ca calmodulindependent protein kinase CaMK C protein kinase C PKC β- β- Wnt Wnt
Wnt Wnt β- PCP Ca CaMK, Ca calmodulin-dependent kinase; Fz, Frizzled, GSK- β; glycogen synthase kinase- β; JNK, c-jun N-terminal kinase; LRP, low density lipoprotein receptorrelated protein ; PKC, protein kinase C; Tcf Lef, T-cell factor lymphoid enhancer factor. C MG Wnt Wnt a Wnt a Wnt a Wnt Wnt Wnt Wnt β- Wnt β- Wnt a Rho Wnt a β- Wnt Wnt Fz Fz low density lipoprotein receptor-related protein LRPLRP receptor tyrosine kinase-like orphan receptor Rorrelated tyrosine kinase orphan receptor Ryk β- Fz LRP LRP Wnt a Fz Ror β- Wnt Wnt Wnt β- adenomatous polyposis coli APC LRP β- Wnt Wnt Wnt Wnt β- Wnt β- T cell factor Lymphocyte enhancing factor Tcf Lefcyclin D c-myc Wnt β- β- APC - β glycogen synthase kinase- β GSK- β Axin Axin α casein kinase α CK α GSK- β
Wnt Wnt CBP, cyclic AMP responsive element binding protein CREB binding protein; sfrp, soluble Frizzled related protein. Wnt Wnt Wnt β- Axin gate keeper gene Axin β- β- cyclin D c-myc β- CK α GSK- β Fbw β- CK α GSK- β β- APC familiar adenomatous polyposis coli FAP APC β- β- FAP APC FAP APC C APC β- Axin β- β-
Axin Axin Axil conductin Axin Axin Axin Axin APC β- GSK- β β- β- β- β- Wnt a β- Wnt a Dukes B Wnt a Wnt a B Wnt a Wnt a Wnt a Wnt a Wnt a diffuse-scattered type Wnt a Wnt a Wnt a Rac Wnt a γ γ Wnt a γ Wnt a Wnt a Wnt a Wnt a Wnt Wnt Wnt Dvl Wnt Wnt Wnt β- Wnt Dickkopf DKK Wnt Fz q Fz GSK- β CAA n GSK- β GSK- β GSK- β q GSK- β T C Wnt GSK- VPA GSK- β- GSK- Wnt GSK- β- GSK- Wnt
GSK- GSK- GSK- βaβ APP PS PS Aβ PS GSK- β- β- PS β- PS β- AMP CREBCBP β- PS β- GSK- APP Aβ Aβ β- Wnt a Aβ Wnt Dkk β- Dvl β- PKC JNK APP β- Aβ ApoE ε E ε ε ApoE ApoE LRP LRP Aβ Wnt LRP ApoE LRP ApoE Wingless Wnt ApoE Wnt LRP β- Wnt Wnt A β- Dkk Wnt receptor activator of NF-κB ligand RANKL osteoprotegerin OPG β- LRP LRP Wnt soluble Fzrelated protein sfrp osteoporosis-pseudoglioma syndrome OPPGLRP OPPG β- sfrp sfrp Wnt Wnt RA RA Wnt Wnt a Fz Wnt a IL- IL- IL- Wnt a RA RANKL Wnt JNK pro-matrix metaroprotease pro-mmp RA Wnt Wnt
Wnt A β- Dkk Wnt RANKL Dkk, Dickkopf ; Sost, Sclerostin; OPG, osteoprotegerin; RANKL, receptor activator of NF-κB ligand. B β- ES Fz RANKL MMP Wnt Wnt β- Bβ- ES Wnt a ES Wnt a ES Wnt β- JNK Fz Fz
Dkk Dvl β- β-β- β- β- Wnt Fz Wnt b Wnt b Dvl β- sfrp infarct rupture Wnt Dvl Wnt LRP EGF LRP Wnt LRP β- Wnt Wnt b Wnt Wnt Wnt a β- β Wnt β- TCF L TCF TCF L TCF L TCF L mrna TCF L mrna Tcf β- glucagon-like peptide GLP GLP β Wnt b Wnt b PPARG peroxisome proliferatorsactivated receptor γ APM adiponectin Wnt b Wnt a Wnt a CaMK PPARγ Wnt a Wnt b β- Wnt Wnt WntWntFz β- β- β- Wnt FEVR FEVR Fz LRP Fz Fz Fz Fz Wnt FEVR
OPPG LRP β- FEVR Fz Norrin Norrin FEVR Wnt autosomal dominant polycystic kidney disease ADPKD PKD PKD β- PKD Wnt Wnt β- Wnt Wnt Wnt Wnt Wnt Wnt β- Wnt Wnt NSAID NSAID NSAID COX FAP Wnt AMP β- COX β- NSAID COX sulindac sulphide FAP β- COX NSAID Wnt APC β- Axin β- Wnt Fz Dvl sfrp Wnt inhibitory factor WIF Wnt Wnt Wnt Wnt Wnt APC β- Axin Wnt sfrp β- Wnt Wnt in vivo β- β- Tcf β- β- E- APC Axin β- Tcf β- PKF- PKF- CGP β- Tcf hot spot β- Tcf in silico β- Tcf PNU- β- CBP BCL pygopus Wnt ICG- CBP
β- PKF- ELISA β- Tcf β- Tcf PKF- ELISA β- Tcf β- Tcf CGP ELISA β- Tcf β- Tcf PNU- β- Tcf ICG- β- Tcf β- CBP β- CBP β- Tcf survivin Wnt Wnt in vitro Wnt ES Wnt ES pluripotency ES ES ES APC ES in vitro ES leukemia inhibitory factor LIF APC ES β- β- ES APC ES ES Tcf Nanog Oct Sox ES Tcf Nanog Oct Sox ES ES β- GSK- BIO Wnt a ES LIF fibroblast growth factor FGF ES Nanog Oct Klf c-myc ips c-myc β- Tcf c-myc Wnt a ips β- ES ips Wnt niche Wnt Tcf Lef
β- Wnt a β- T B HoxB β- HoxB niche Dkk β- β- β- niche Tcf β- β- Tcf Lgr G Tcf EphB ephrinb β- ephrinb EphB EphB β- ephrinb EphB Wnt Wnt Wnt Wnt Wnt β- Tcf Wnt Wnt Wnt Wnt Wnt Logan, C.Y. & Nusse, R.Annu. Rev. Cell Dev. Biol.,, Kikuchi, A., Yamamoto, H., & Kishida, S.Cell. Signal.,, Veeman, M.T., Axelrod, J.D., & Moon, R.T.Dev. Cell,,
Kikuchi, A. & Yamamoto, H.Cancer Sci.,,. Kishida, S., Yamamoto, H., & Kikuchi, A.Mol. Cell. Biol.,, Mikels,A.J.&Nusse,R.PLoS Biol.,, He, X., Semënov, M., Tamai, K., & Zeng, X.Development,, Wang, H.Y., Liu, T., & Malbon, C.C.Cell. Signal.,, Green, J.L., Kuntz, S.G., & Sternberg, P.W.Trends Cell Biol.,, Yamamoto, S., Nishimura, O., Misaki, K., Nishita, M., Minami, Y., Yonemura, S., Tarui, H., & Sasaki, H.Dev. Cell,,. Kikuchi, A., Yamamoto, H., & Sato, A.Trends Cell Biol.,, van Amerongen, R., Mikels, A., & Nusse, R.Sci. Signal,, re. Yamamoto, H., Komekado, H., & Kikuchi, A.Dev. Cell,, Yamamoto, H., Sakane, H., Yamamoto, H., Michiue, T., & Kikuchi, A.Dev. Cell,,. Moon, R.T., Kohn, A.D., De Ferrari, G.V., & Kaykas, A. Nat. Rev. Genet.,, Maiese, K., Li, F., Chong, Z.Z., & Shang, Y.C.Pharmacol. Ther.,,. Barker, N. & Clevers, H.Nat. Rev. Drug Discov.,, Ikeda, S., Kishida, S., Yamamoto, H., Murai, H., Koyama, S., & Kikuchi, A.EMBO J.,, Kitagawa, M., Hatakeyama, S., Shirane, M., Matsumoto, M., Ishida, N., Hattori, K., Nakamichi, I., Kikuchi, A., Nakayama, K.-I., & Nakayama, K.EMBO J.,, Liu, C., Li, Y., Semenov, M., Han, C., Baeg, G.-H., Tan, Y., Zhang, Z., Lin, X., & He, X.Cell,, Nusse,R.&Varmus,H.E.Cell,,. Polakis, P.Genes Dev.,, Su, Y., Fu, C., Ishikawa, S., Stella, A., Kojima, M., Shitoh, K., Schreiber, E.M., Day, B.W., & Liu, B.Mol. Cell,, Kishida, S., Yamamoto, H., Ikeda, S., Kishida, M., Sakamoto, I., Koyama, S., & Kikuchi, A.J. Biol. Chem.,, Hinoi, T., Yamamoto, H., Kishida, M., Takada, S., Kishida, S., & Kikuchi, A.J. Biol. Chem.,, Yamamoto,H.,Kishida,S.,Uochi,T.,Ikeda,S.,Koyama,S., Asashima, M., & Kikuchi, A.Mol. Cell. Biol.,, Satoh, S., Daigo, Y., Furukawa, Y., Kato, T., Miwa, N., Nishiwaki, T., Kawasoe, T., Ishiguro, H., Fujita, M., Tokino, T., Sasaki, Y., Imaoka, S., Murata, M., Shimano, T., Yamaoka, Y., & Nakamura, Y.Nat. Genet.,, Liu, W., Dong, X., Mai, M., Seelan, R.S., Taniguchi, K., Krishnadath, K.K., Halling, K.C., Cunningham, J.M., Qian, C., Christensen, E., Roche, P.C., Smith, D.I., & Thibodeau, S.N.Nat. Genet.,, Kremenevskaja, N., von Wasielewski, R., Rao, A.S., Schofl, C., Andersson, T., & Brabant, G. Oncogene,, Dejmek, J., Dejmek, A., Safholm, A., Sjolander, A., & Andersson, T.Cancer Res.,, Liang, H., Chen, Q., Coles, A.H., Anderson, S.J., Pihan, G., Bradley, A., Gerstein, R., Jurecic, R., & Jones, S.N. Cancer Cell,, Weeraratna, A.T., Jiang, Y., Hostetter, G., Rosenblatt, K., Duray, P., Bittner, M., & Trent, J.M.Cancer Cell,, Huang, C.L., Liu, D., Nakano, J., Ishikawa, S., Kontani, K., Yokomise, H., & Ueno, M.J. Clin. Oncol.,,. Kurayoshi, M., Oue, N., Yamamoto, H., Kishida, M., Inoue, A., Asahara, T., Yasui, W., & Kikuchi, A.Cancer Res.,, Yamamoto, H., Kitadai, Y., Yamamoto, H., Oue, N., Odan, H., Yasui, W., & Kikuchi, A.Gastroenterology,, Miyazaki, K.Cancer Sci.,,. Wilson, S.W. & Houart, C.Dev. Cell,, Ciani, L. & Salinas, P.C.Nat. Rev. Neurosci.,,. Lijam, N., Paylor, R., McDonald, M.P., Crawley, J.N., Deng, C.X., Herrup, K., Stevens, K.E., Maccaferri, G., McBain, C.J., Sussman, D.J., & Wynshaw-Boris, A.Cell,,. Rapoport, J.L., Addington, A.M., Frangou, S., & Psych, M.R. Mol. Psychiatry,, Miyaoka, T., Seno, H., & Ishino, H.Schizophr. Res.,,. Ftouh, S., Akbar, M.T., Hirsch, S.R., & de Belleroche, J.S. J. Neurochem.,, Katsu, T., Ujike, H., Nakano, T., Tanaka, Y., Nomura, A., Nakata, K., Takaki, M., Sakai, A., Uchida, N., Imamura, T., & Kuroda, S.Neurosci. Lett.,,. Scassellati, C., Bonvicini, C., Perez, J., Bocchio-Chiavetto, L., Tura, G.B., Rossi, G., Racagni, G., & Gennarelli, M. Neuropsychobiology,,. Kozlovsky, N., Belmaker, R.H., & Agam, G.Am. J. Psychiatry,, Kozlovsky, N., Belmaker, R.H., & Agam, G.Eur. Neuropsychopharmacol.,,. Bailer, U., Leisch, F., Meszaros, K., Lenzinger, E., Willinger, U.,Strobl,R.,Heiden,A.,Gebhardt,C.,Doge,E.,Fuchs,K., Sieghart, W., Kasper, S., Hornik, K., & Aschauer, H.N. Biol. Psychiatry,,. Benedetti, F., Serretti, A., Pontiggia, A., Bernasconi, A., Lorenzi, C., Colombo, C., & Smeraldi, E.Neurosci. Lett.,,. Svenningsson, P., Tzavara, E.T., Carruthers, R., Rachleff, I., Wattler, S., Nehls, M., McKinzie, D.L., Fienberg, A.A., Nomikos, G.G., & Greengard, P.Science,,. Hardy, J. & Selkoe, D.J.Science,, Doble, B.W. & Woodgett, J.R.J. Cell Sci.,, Soriano, S., Kang, D.E., Fu, M., Pestell, R., Chevallier, N., Zheng, H., & Koo, E.H.J. Cell Biol.,, Kang, D.E., Soriano, S., Xia, X., Eberhart, C.G., De Strooper, B., Zheng, H., & Koo, E.H.Cell,, Teo, J.L., Ma, H., Nguyen, C., Lam, C., & Kahn, M. Proc. Natl. Acad. Sci. USA,, Zhang, Z., Hartmann, H., Do, V.M., Abramowski, D., Sturchler-Pierrat, C., Staufenbiel, M., Sommer, B., van de Wetering, M., Clevers, H., Saftig, P., De Strooper, B., He, X., & Yankner, B.A.Nature,,
De Ferrari, G.V., Chacon, M.A., Barria, M.I., Garrido, J.L., Godoy, J.A., Olivares, G., Reyes, A.E., Alvarez, A., Bronfman, M., & Inestrosa, N.C.Mol. Psychiatry,, Alvarez, A.R., Godoy, J.A., Mullendorff, K., Olivares, G.H., Bronfman, M., & Inestrosa, N.C.Exp. Cell Res.,, Mudher, A., Chapman, S., Richardson, J., Asuni, A., Gibb, G., Pollard, C., Killick, R., Iqbal, T., Raymond, L., Varndell, I., Sheppard, P., Makoff, A., Gower, E., Soden, P.E., Lewis, P., Murphy, M., Golde, T.E., Rupniak, H.T., Anderton, B.H., & Lovestone, S.J. Neurosci.,, Corder, E.H., Saunders, A.M., Strittmatter, W.J., Schmechel, D.E.,Gaskell,P.C.,Small,G.W.,Roses,A.D.,Haines,J.L.,& Pericak-Vance, M.A.Science,, Kang, D.E., Pietrzik, C.U., Baum, L., Chevallier, N., Merriam, D.E., Kounnas, M.Z., Wagner, S.L., Troncoso, J.C., Kawas, C.H., Katzman, R., & Koo, E.H.J. Clin. Invest.,, Magoori, K., Kang, M.J., Ito, M.R., Kakuuchi, H., Ioka, R.X., Kamataki, A., Kim, D.H., Asaba, H., Iwasaki, S., Takei, Y.A., Sasaki, M., Usui, S., Okazaki, M., Takahashi, S., Ono, M., Nose, M., Sakai, J., Fujino, T., & Yamamoto, T.T.J. Biol. Chem.,, De Ferrari, G.V., Papassotiropoulos, A., Biechele, T., Wavrant De-Vrieze, F., Avila, M.E., Major, M.B., Myers, A., Saez, K., Henriquez, J.P., Zhao, A., Wollmer, M.A., Nitsch, R.M., Hock, C., Morris, C.M., Hardy, J., & Moon, R.T. Proc. Natl. Acad. Sci. USA,, Panakova, D., Sprong, H., Marois, E., Thiele, C., & Eaton, S. Nature,,. Harada, S. & Rodan, G.A.Nature,, Boyden, L.M., Mao, J., Belsky, J., Mitzner, L., Farhi, A., Mitnick, M.A., Wu, D., Insogna, K., & Lifton, R.P.N. Engl.J.Med.,, Zhang, Y., Wang, Y., Li, X., Zhang, J., Mao, J., Li, Z., Zheng, J., Li, L., Harris, S., & Wu, D.Mol. Cell. Biol.,, Bodine, P.V., Zhao, W., Kharode, Y.P., Bex, F.J., Lambert, A.J.,Goad,M.B.,Gaur,T.,Stein,G.S.,Lian,J.B.,&Komm, B.S.Mol. Endocrinol.,, Gong, Y., Slee, R.B., Fukai, N., Rawadi, G., Roman-Roman, S., Reginato, A.M., Wang, H., Cundy, T., Glorieux, F.H., Lev, D., Zacharin, M., Oexle, K., Marcelino, J., Suwairi, W., Heeger, S., Sabatakos, G., Apte, S., Adkins, W.N., Allgrove, J., Arslan-Kirchner, M., Batch, J.A., Beighton, P., Black, G.C., Boles, R.G., Boon, L.M., Borrone, C., Brunner, H.G., Carle, G.F., Dallapiccola, B., De Paepe, A., Floege, B., Halfhide, M.L., Hall, B., Hennekam, R.C., Hirose, T., Jans, A., Juppner, H., Kim, C.A., Keppler-Noreuil, K., Kohlschuetter, A., LaCombe, D., Lambert, M., Lemyre, E., Letteboer, T., Peltonen, L., Ramesar, R.S., Romanengo, M., Somer, H., Steichen-Gersdorf, E., Steinmann, B., Sullivan, B., Superti- Furga, A., Swoboda, W., van den Boogaard, M.J., Van Hul, W., Vikkula, M., Votruba, M., Zabel, B., Garcia, T., Baron, R., Olsen, B.R., & Warman, M.L.Cell,,. Loughlin, J., Dowling, B., Chapman, K., Marcelline, L., Mustafa, Z., Southam, L., Ferreira, A., Ciesielski, C., Carson, D.A., & Corr, M. Proc. Natl. Acad. Sci. USA,, Sen, M., Lauterbach, K., El-Gabalawy, H., Firestein, G.S., Corr, M., & Carson, D.A.Proc. Natl. Acad. Sci. USA,, Sen, M., Reifert, J., Lauterbach, K., Wolf, V., Rubin, J.S., Corr, M., & Carson, D.A.Arthritis Rheum.,,. Tzahor, E.Dev. Cell,,. Kwon, C., Arnold, J., Hsiao, E.C., Taketo, M.M., Conklin, B.R., & Srivastava, D.Proc. Natl. Acad. Sci. USA,, Bakre, M.M., Hoi, A., Mong, J.C., Koh, Y.Y., Wong, K.Y., & Stanton, L.W.J. Biol. Chem.,, Naito, A.T., Shiojima, I., Akazawa, H., Hidaka, K., Morisaki, T., Kikuchi, A., & Komuro, I.Proc. Natl. Acad. Sci. USA,, Pandur, P., Lasche, M., Eisenberg, L.M., & Kuhl, M. Nature,, van de Schans, V.A., Smits, J.F., & Blankesteijn, W.M. Eur. J. Pharmacol.,, Cerutti, C., Kurdi, M., Bricca, G., Hodroj, W., Paultre, C., Randon, J., & Gustin, M.P.Physiol. Genomics,, Haq, S., Michael, A., Andreucci, M., Bhattacharya, K., Dotto, P., Walters, B., Woodgett, J., Kilter, H., & Force, T. Proc. Natl. Acad. Sci. USA,, Qu, J., Zhou, J., Yi, X.P., Dong, B., Zheng, H., Miller, L.M., Wang, X., Schneider, M.D., & Li, F.J. Mol. Cell. Cardiol.,, Blankesteijn, W.M., Essers-Janssen, Y.P., Verluyten, M.J., Daemen, M.J., & Smits, J.F.Nat. Med.,, Blankesteijn, W.M., van Gijn, M.E., Essers-Janssen, Y.P., Daemen, M.J., & Smits, J.F.Am. J. Pathol.,, Barandon, L., Couffinhal, T., Ezan, J., Dufourcq, P., Costet, P., Alzieu, P., Leroux, L., Moreau, C., Dare, D., & Duplaa, C. Circulation,, van Gijn, M.E., Daemen, M.J., Smits, J.F., & Blankesteijn, W.M.Cardiovasc. Res.,,. Mani, A., Radhakrishnan, J., Wang, H., Mani, M.A., Nelson- Williams, C., Carew, K.S., Mane, S., Najmabadi, H., Wu, D., & Lifton, R.P.Science,, Wright, W.S., Longo, K.A., Dolinsky, V.W., Gerin, I., Kang, S., Bennett, C.N., Chiang, S.H., Prestwich, T.C., Gress, C., Burant, C.F., Susulic, V.S., & MacDougald, O.A. Diabetes,, Chong, Z.Z., Shang, Y.C., & Maiese, K.Curr. Neurovasc. Res.,, Rulifson, I.C., Karnik, S.K., Heiser, P.W., ten Berge, D., Chen, H., Gu, X., Taketo, M.M., Nusse, R., Hebrok, M., & Kim, S.K.Proc. Natl. Acad. Sci. USA,,. O Rahilly, S. & Wareham, N.J.N. Engl. J. Med.,, Lyssenko, V., Lupi, R., Marchetti, P., Del Guerra, S., Orho- Melander, M., Almgren, P., Sjogren, M., Ling, C., Eriksson, K.F., Lethagen, A.L., Mancarella, R., Berglund, G., Tuomi, T., Nilsson, P., Del Prato, S., & Groop, L.J. Clin. Invest.,, Yi, F., Brubaker, P.L., & Jin, T.J. Biol. Chem.,, Kanazawa, A., Tsukada, S., Sekine, A., Tsunoda, T., Takahashi, A., Kashiwagi, A., Tanaka, Y., Babazono, T., Matsuda, M., Kaku, K., Iwamoto, Y., Kawamori, R., Kikkawa, R.,
Nakamura, Y., & Maeda, S.Am.J.Hum.Genet.,, Takada, I., Mihara, M., Suzawa, M., Ohtake, F., Kobayashi, S., Igarashi, M., Youn, M.Y., Takeyama, K., Nakamura, T., Mezaki, Y., Takezawa, S., Yogiashi, Y., Kitagawa, H., Yamada, G., Takada, S., Minami, Y., Shibuya, H., Matsumoto, K., & Kato, S.Nat. Cell Biol.,, Masckauchan, T.N. & Kitajewski, J.Physiology Bethesda,, Blankesteijn, W.M., van Gijn, M.E., Essers-Janssen, Y.P., Daemen, M.J., & Smits, J.F.Am. J. Pathol.,, Easwaran, V., Lee, S.H., Inge, L., Guo, L., Goldbeck, C., Garrett, E., Wiesmann, M., Garcia, P.D., Fuller, J.H., Chan, V., Randazzo, F., Gundel, R., Warren, R.S., Escobedo, J., Aukerman, S.L., Taylor, R.N., & Fantl, W.J.Cancer Res.,, Robitaille, J., MacDonald, M.L., Kaykas, A., Sheldahl, L.C., Zeisler, J., Dube, M.P., Zhang, L.H., Singaraja, R.R., Guernsey, D.L., Zheng, B., Siebert, L.F., Hoskin-Mott, A., Trese, M.T., Pimstone, S.N., Shastry, B.S., Moon, R.T., Hayden, M.R., Goldberg, Y.P., & Samuels, M.E.Nat. Genet.,, Kondo, H., Hayashi, H., Oshima, K., Tahira, T., & Hayashi, K.Br. J. Ophthalmol.,, Kaykas, A., Yang-Snyder, J., Heroux, M., Shah, K.V., Bouvier, M., & Moon, R.T.Nat. Cell Biol.,,. Xu, Q., Wang, Y., Dabdoub, A., Smallwood, P.M., Williams, J., Woods, C., Kelley, M.W., Jiang, L., Tasman, W., Zhang, K., & Nathans, J.Cell,, Rodova, M., Islam, M.R., Maser, R.L., & Calvet, J.P. J. Biol. Chem.,, Perantoni, A.O.Semin. Cell Dev. Biol.,, Terada, Y., Tanaka, H., Okado, T., Shimamura, H., Inoshita, S., Kuwahara, M., & Sasaki, S.J. Am. Soc. Nephrol.,, Giovannucci, E., Rimm, E.B., Stampfer, M.J., Colditz, G.A., Ascherio, A., & Willett, W.C.Ann. Intern. Med.,, Castellone, M.D., Teramoto, H., Williams, B.O., Druey, K.M., & Gutkind, J.S.Science,, Hino, S., Tanji, C., Nakayama, K.-I., & Kikuchi, A. Mol. Cell. Biol.,, Boon, E.M., Keller, J.J., Wormhoudt, T.A., Giardiello, F.M., Offerhaus, G.J., van der Neut, R., & Pals, S.T.Br. J. Cancer,, Suzuki, H., Watkins, D.N., Jair, K.W., Schuebel, K.E., Markowitz, S.D., Dong Chen, W., Pretlow, T.P., Yang, B., Akiyama, Y., Van Engeland, M., Toyota, M., Tokino, T., Hinoda, Y., Imai, K., Herman, J.G., & Baylin, S.B. Nat. Genet.,, Rhee, C.S., Sen, M., Lu, D., Wu, C., Leoni, L., Rubin, J., Corr, M., & Carson, D.A.Oncogene,, He, B., You, L., Uematsu, K., Xu, Z., Lee, A.Y., Matsangou, M., McCormick, F., & Jablons, D.M.Neoplasia,,. He, B., Reguart, N., You, L., Mazieres, J., Xu, Z., Lee, A.Y., Mikami, I., McCormick, F., & Jablons, D.M.Oncogene,, Graham, T.A., Weaver, C., Mao, F., Kimelman, D., & Xu, W. Cell,, von Kries, J.P., Winbeck, G., Asbrand, C., Schwarz-Romond, T., Sochnikova, N., Dell Oro, A., Behrens, J., & Birchmeier, W.Nat. Struct. Biol.,, Lepourcelet, M., Chen, Y.N., France, D.S., Wang, H., Crews, P., Petersen, F., Bruseo, C., Wood, A.W., & Shivdasani, R.A. Cancer Cell,,. Trosset, J.Y., Dalvit, C., Knapp, S., Fasolini, M., Veronesi, M., Mantegani, S., Gianellini, L.M., Catana, C., Sundstrom, M., Stouten, P.F., & Moll, J.K.Proteins,,. Hecht, A., Vleminckx, K., Stemmler, M.P., van Roy, F., & Kemler, R.EMBO J.,, Kramps, T., Peter, O., Brunner, E., Nellen, D., Froesch, B., Chatterjee, S., Murone, M., Zullig, S., & Basler, K. Cell,,. Emami, K.H., Nguyen, C., Ma, H., Kim, D.H., Jeong, K.W., Eguchi, M., Moon, R.T., Teo, J.L., Kim, H.Y., Moon, S.H., Ha, J.R., & Kahn, M.Proc. Natl. Acad. Sci. USA,, Evans, M.J. & Kaufman, M.H.Nature,, Kielman, M.F., Rindapaa, M., Gaspar, C., van Poppel, N., Breukel, C., van Leeuwen, S., Taketo, M.M., Roberts, S., Smits, R., & Fodde, R.Nat. Genet.,, Pereira, L., Yi, F., & Merrill, B.J.Mol. Cell. Biol.,, Boyer, L.A., Lee, T.I., Cole, M.F., Johnstone, S.E., Levine, S.S., Zucker, J.P., Guenther, M.G., Kumar, R.M., Murray, H.L., Jenner, R.G., Gifford, D.K., Melton, D.A., Jaenisch, R., & Young, R.A.Cell,, Cole, M.F., Johnstone, S.E., Newman, J.J., Kagey, M.H., & Young, R.A.Genes Dev.,, Sato, N., Meijer, L., Skaltsounis, L., Greengard, P., & Brivanlou, A.H.Nat. Med.,,. Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S.Cell,, Marson, A., Foreman, R., Chevalier, B., Bilodeau, S., Kahn, M., Young, R.A., & Jaenisch, R.Cell Stem Cell,, Potten, C.S. & Loeffler, M.Development,,. Willert, K., Brown, J.D., Danenberg, E., Duncan, A.W., Weissman, I.L., Reya, T., Yates, J.R.I., & Nusse, R. Nature,, Reya, T., Duncan, A.W., Ailles, L., Domen, J., Scherer, D.C., Willert, K., Hintz, L., Nusse, R., & Weissman, I.L. Nature,, Antonchuk, J., Sauvageau, G., & Humphries, R.K. Cell,,. Fleming, H.E., Janzen, V., Lo Celso, C., Guo, J., Leahy, K.M., Kronenberg, H.M., & Scadden, D.T.Cell Stem Cell,, Jeannet, G., Scheller, M., Scarpellino, L., Duboux, S., Gardiol, N., Back, J., Kuttler, F., Malanchi, I., Birchmeier, W., Leutz, A., Huelsken, J., & Held, W.Blood,, Koch, U., Wilson, A., Cobas, M., Kemler, R., Macdonald, H.R., & Radtke, F.Blood,, He, X.C., Zhang, J., Tong, W.G., Tawfik, O., Ross, J., Scoville, D.H., Tian, Q., Zeng, X., He, X., Wiedemann, L.M., Mishina,Y.,&Li,L.Nat. Genet.,, Barker,N.,vanEs,J.H.,Kuipers,J.,Kujala,P.,vandenBorn, M., Cozijnsen, M., Haegebarth, A., Korving, J., Begthel, H., Peters, P.J., & Clevers, H.Nature,, Batlle, E., Henderson, J.T., Beghtel, H., van den Born, M.M., Sancho, E., Huls, G., Meeldijk, J., Robertson, J., van de Wetering, M., Pawson, T., & Clevers, H.Cell,,