A novel tankyrase inhibitor decreases canonical Wnt signaling in colon carcinoma cells and reduces tumor growth in conditional APC mutant mice
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F12%3A00383115" target="_blank" >RIV/68378050:_____/12:00383115 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1158/0008-5472.CAN-11-3336" target="_blank" >http://dx.doi.org/10.1158/0008-5472.CAN-11-3336</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1158/0008-5472.CAN-11-3336" target="_blank" >10.1158/0008-5472.CAN-11-3336</a>
Alternative languages
Result language
angličtina
Original language name
A novel tankyrase inhibitor decreases canonical Wnt signaling in colon carcinoma cells and reduces tumor growth in conditional APC mutant mice
Original language description
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 Xenop
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
EB - Genetics and molecular biology
OECD FORD branch
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Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
Z - Vyzkumny zamer (s odkazem do CEZ)
Others
Publication year
2012
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cancer Research
ISSN
0008-5472
e-ISSN
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Volume of the periodical
72
Issue of the periodical within the volume
11
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
2822-2832
UT code for WoS article
000307348000015
EID of the result in the Scopus database
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