Breast cancer-specific mutations in CK1epsilon inhibit Wnt/beta-catenin and activate the Wnt/Rac1/JNK and NFAT pathways to decrease cell adhesion and promote cell migration

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F10%3A00352336" target="_blank" >RIV/60077344:_____/10:00352336 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68081707:_____/10:00352336 RIV/60076658:12310/10:00012040 RIV/00216224:14310/10:00067265

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Breast cancer-specific mutations in CK1epsilon inhibit Wnt/beta-catenin and activate the Wnt/Rac1/JNK and NFAT pathways to decrease cell adhesion and promote cell migration

Popis výsledku v původním jazyce

In silico modeling and in vivo data showed that autophosphorylation at Thr 44, a site adjacent to the breast cancer point mutations in the N-terminal lobe of human CK1-epsilon, is involved in positive regulation of the CK1-epsilon activity. Our data further demonstrate that, in mammalian cells, mutated forms of CK1-epsilon failed to affect the intracellular localization and phosphorylation of Dvl2; we were able to demonstrate that CK1? mutants were unable to enhance Dvl-induced TCF/LEF-mediated transcription, that CK1-epsilon mutants acted as loss-of-function in the Wnt/beta-catenin pathway, and that CK1-epsilon mutants activated the noncanonical Wnt/Rac-1 and NFAT pathways, similar to pharmacological inhibitors of CK1. In line with these findings, inhibition of CK1 promoted cell migration as well as decreased cell adhesion and E-cadherin expression in the breast cancer-derived cell line MCF7.

Název v anglickém jazyce

Breast cancer-specific mutations in CK1epsilon inhibit Wnt/beta-catenin and activate the Wnt/Rac1/JNK and NFAT pathways to decrease cell adhesion and promote cell migration

Popis výsledku anglicky

In silico modeling and in vivo data showed that autophosphorylation at Thr 44, a site adjacent to the breast cancer point mutations in the N-terminal lobe of human CK1-epsilon, is involved in positive regulation of the CK1-epsilon activity. Our data further demonstrate that, in mammalian cells, mutated forms of CK1-epsilon failed to affect the intracellular localization and phosphorylation of Dvl2; we were able to demonstrate that CK1? mutants were unable to enhance Dvl-induced TCF/LEF-mediated transcription, that CK1-epsilon mutants acted as loss-of-function in the Wnt/beta-catenin pathway, and that CK1-epsilon mutants activated the noncanonical Wnt/Rac-1 and NFAT pathways, similar to pharmacological inhibitors of CK1. In line with these findings, inhibition of CK1 promoted cell migration as well as decreased cell adhesion and E-cadherin expression in the breast cancer-derived cell line MCF7.

Druh

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

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2010

Kód důvěrnosti údajů

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

Název periodika

Breast Cancer Research

ISSN

1465-5411

e-ISSN

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Svazek periodika

2010

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

14

Strana od-do

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Kód UT WoS článku

000285689000006

EID výsledku v databázi Scopus

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