. . . "000307348000015" . "A novel tankyrase inhibitor decreases canonical Wnt signaling in colon carcinoma cells and reduces tumor growth in conditional APC mutant mice"@en . "Voronkov, A." . "Increased nuclear accumulation of beta-catenin, a mediator of canonical Wnt signaling, is found in numerous tumors and is frequently associated with tumor progression and metastasis. Inhibition of Wnt/beta-catenin signaling therefore is an attractive strategy for anticancer drugs. In this study, we have identified a novel small molecule inhibitor of the beta-catenin signaling pathway, JW55, that functions via inhibition of the PARP domain of tankyrase 1 and tankyrase 2 (TNKS1/2), regulators of the beta-catenin destruction complex. Inhibition of TNKS1/2 poly(ADP-ribosyl) ation activity by JW55 led to stabilization of AXIN2, a member of the beta-catenin destruction complex, followed by increased degradation of beta-catenin. In a dose-dependent manner, JW55 inhibited canonical Wnt signaling in colon carcinoma cells that contained mutations in either the APC (adenomatous polyposis coli) locus or in an allele of beta-catenin. In addition, JW55 reduced XWnt8-induced axis duplication in Xenopus embryos and tamoxifen-induced polyposis formation in conditional APC mutant mice. Together, our findings provide a novel chemotype for targeting canonical Wnt/beta-catenin signaling through inhibiting the PARP domain of TNKS1/2." . . "Increased nuclear accumulation of beta-catenin, a mediator of canonical Wnt signaling, is found in numerous tumors and is frequently associated with tumor progression and metastasis. Inhibition of Wnt/beta-catenin signaling therefore is an attractive strategy for anticancer drugs. In this study, we have identified a novel small molecule inhibitor of the beta-catenin signaling pathway, JW55, that functions via inhibition of the PARP domain of tankyrase 1 and tankyrase 2 (TNKS1/2), regulators of the beta-catenin destruction complex. Inhibition of TNKS1/2 poly(ADP-ribosyl) ation activity by JW55 led to stabilization of AXIN2, a member of the beta-catenin destruction complex, followed by increased degradation of beta-catenin. In a dose-dependent manner, JW55 inhibited canonical Wnt signaling in colon carcinoma cells that contained mutations in either the APC (adenomatous polyposis coli) locus or in an allele of beta-catenin. In addition, JW55 reduced XWnt8-induced axis duplication in Xenopus embryos and tamoxifen-induced polyposis formation in conditional APC mutant mice. Together, our findings provide a novel chemotype for targeting canonical Wnt/beta-catenin signaling through inhibiting the PARP domain of TNKS1/2."@en . "beta-catenin; canonical Wnt signaling; tankyrase; inhibition"@en . . "Paulsen, J. E." . . "Ko\u0159\u00EDnek, Vladim\u00EDr" . "[EE178C34427A]" . "120485" . "P(2B06077), P(GAP305/12/2042), Z(AV0Z50520514)" . "14"^^ . "Eide, T. J." . "Gradl, D." . . "11"^^ . "Macho\u0148, Ond\u0159ej" . "T\u016Fmov\u00E1, Lucie" . . . . "72" . "0008-5472" . . "von Kries, J. P." . "Cancer Research" . . . "11" . "RIV/68378050:_____/12:00383115!RIV13-GA0-68378050" . . "RIV/68378050:_____/12:00383115" . "Wilson, S. R." . "Dinh, H." . "A novel tankyrase inhibitor decreases canonical Wnt signaling in colon carcinoma cells and reduces tumor growth in conditional APC mutant mice" . . . . "4"^^ . . . "10.1158/0008-5472.CAN-11-3336" . "Macho\u0148ov\u00E1, Olga" . "US - Spojen\u00E9 st\u00E1ty americk\u00E9" . "A novel tankyrase inhibitor decreases canonical Wnt signaling in colon carcinoma cells and reduces tumor growth in conditional APC mutant mice"@en . . . "A novel tankyrase inhibitor decreases canonical Wnt signaling in colon carcinoma cells and reduces tumor growth in conditional APC mutant mice" . "Pedersen, N. M." . . . "Krauss, S." . "Waaler, J." .