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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

SYSNO ASEP	0352336
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	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
Author(s)	Foldynová-Trantírková, Silvie (BC-A)_RID Sekyrová, Petra (BC-A) Tmejová, Kateřina (BFU-R) Brumovská, E. (CZ) Bernatik, O. (CZ) Blankenfeldt, W. (DE) Krejčí, Pavel (BFU-R) Kozubík, Alois (BFU-R)_{RID, ORCID} Doležal, Tomáš (BC-A) Trantírek, Lukáš (BC-A) Bryja, Vítězslav (BFU-R)_{RID, ORCID}
Source Title	Breast Cancer Research - ISSN 1465-5411 Roč. 2010, č. 3 (2010), R30
Number of pages	14 s.
Language	eng - English
Country	GB - United Kingdom
Keywords	casein kinase 1 epsilon ; Wnt signaling cascade ; kinase activity ; autophosphorylation
Subject RIV	EB - Genetics ; Molecular Biology
R&D Projects	GA301/07/0814 GA ČR - Czech Science Foundation (CSF)
	GD204/09/H058 GA ČR - Czech Science Foundation (CSF)
CEZ	AV0Z60220518 - PAU-O, BC-A (2005-2011)
	AV0Z50070508 - ENTU-I, BC-A (2005-2011)
	AV0Z50040507 - BFU-R (2005-2011)
	AV0Z50040702 - BFU-R (2007-2013)
UT WOS	000285689000006
DOI	10.1186/bcr2581
Annotation	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 CK1ε 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.
Workplace	Biology Centre (since 2006)
Contact	Dana Hypšová, eje@eje.cz, Tel.: 387 775 214
Year of Publishing	2011

Number of the records: 1