FMP Publications

Our publications are recorded in a searchable database since 2010, updates will be added regularly.

Year:  
All :: 2012
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All :: Waaler(*), Waberski(*), Wachten(*), Wade(*), ... , Wynn(*) 
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References
A Novel Tankyrase Inhibitor Decreases Canonical Wnt Signaling in Colon Carcinoma Cells and Reduces Tumor Growth in Conditional APC Mutant Mice
Waaler(*), J., Machon(*), O., Tumova(*), L., Dinh(*), H., Korinek(*), V., Wilson(*), S. R., Paulsen(*), J. E., Pedersen(*), N. M., Eide(*), T. J., Machonova(*), O., Gradl(*), D., Voronkov(*), A., von Kries, J. P.; Krauss(*), S.
Cancer research, 72:2822-2832
(2012)

Tags: Screening Unit (von Kries)

Abstract: 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. Cancer Res; 72(11); 2822-32. (C)2012 AACR.

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Leibniz-Forschungsinstitut für Molekulare Pharmakologie im Forschungsverbund Berlin e.V. (FMP)
Campus Berlin-Buch
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