Novel synthetic antagonists of canonical Wnt signaling inhibit colorectal cancer cell growth
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F11%3A00371840" target="_blank" >RIV/68378050:_____/11:00371840 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1158/0008-5472.CAN-10-1282" target="_blank" >http://dx.doi.org/10.1158/0008-5472.CAN-10-1282</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1158/0008-5472.CAN-10-1282" target="_blank" >10.1158/0008-5472.CAN-10-1282</a>
Alternative languages
Result language
angličtina
Original language name
Novel synthetic antagonists of canonical Wnt signaling inhibit colorectal cancer cell growth
Original language description
Canonical Wnt signaling is deregulated in several types of human cancer where it plays a central role in tumor cell growth and progression. Here we report the identification of 2 new small molecules that specifically inhibit canonical Wnt pathway at thelevel of the destruction complex. Specificity was verified in various cellular reporter systems, a Xenopus double-axis formation assay and a gene expression profile analysis. In human colorectal cancer (CRC) cells, the new compounds JW67 and JW74 rapidlyreduced active beta-catenin with a subsequent downregulation of Wnt target genes, including AXIN2, SP5, and NKD1. Notably, AXIN2 protein levels were strongly increased after compound exposure. Long-term treatment with JW74 inhibited the growth of tumorcells in both a mouse xenograft model of CRC and in Apc(Min) mice (multiple intestinal neoplasia, Min). Our findings rationalize further preclinical and clinical evaluation of these new compounds as novel modalities for cancer treatment.
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
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Continuities
Z - Vyzkumny zamer (s odkazem do CEZ)
Others
Publication year
2011
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
71
Issue of the periodical within the volume
1
Country of publishing house
US - UNITED STATES
Number of pages
9
Pages from-to
197-205
UT code for WoS article
000285826800022
EID of the result in the Scopus database
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