Novel synthetic antagonists of canonical Wnt signaling inhibit colorectal cancer cell growth

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Novel synthetic antagonists of canonical Wnt signaling inhibit colorectal cancer cell growth

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Novel synthetic antagonists of canonical Wnt signaling inhibit colorectal cancer cell growth

Popis výsledku anglicky

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.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

—

Projekt

—

Návaznosti

Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2011

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Cancer Research

ISSN

0008-5472

e-ISSN

—

Svazek periodika

71

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

197-205

Kód UT WoS článku

000285826800022

EID výsledku v databázi Scopus

—