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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
- 1.0352336 - BC 2011 RIV GB eng J - Journal Article
Foldynová-Trantírková, Silvie - Sekyrová, Petra - Tmejová, Kateřina - Brumovská, E. - Bernatik, O. - Blankenfeldt, W. - Krejčí, Pavel - Kozubík, Alois - Doležal, Tomáš - Trantírek, Lukáš - Bryja, Vítězslav
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.
Breast Cancer Research. Roč. 2010, č. 3 (2010), R30. ISSN 1465-5411. E-ISSN 1465-542X
R&D Projects: GA ČR GA301/07/0814; GA ČR(CZ) GD204/09/H058
Grant - others:GA ČR(CZ) GA204/09/0498; GA ČR(CZ) GA301/09/0587; GA ČR(CZ) KJB501630801
Institutional research plan: CEZ:AV0Z60220518; CEZ:AV0Z50070508; CEZ:AV0Z50040507; CEZ:AV0Z50040702
Keywords : casein kinase 1 epsilon * Wnt signaling cascade * kinase activity * autophosphorylation
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 5.785, year: 2010
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.
Permanent Link: http://hdl.handle.net/11104/0191864
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