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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

  • Czech description

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

Result continuities

  • Project

  • 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

  • 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