Régulation du facteur de transcription SNAIL1 au cours de la Transition Epithélio-Mésenchymateuse dans les cellules mammaires MCF10A : implication de la protéine-kinase CK2

Abstract : Epithelial cells are key components for a plethora of vital functions in mammals, in particular because they can polarize and cohesively interact in a dynamic manner. These properties, grouped under the term of « Epithelial plasticity », can manifest themselves in different ways of which the most complex is Epithelial-Mesenchymal Transition (EMT), a process that drives a cohesive epithelial cell (or a group of cells) to strongly modify its organization and its protein composition, in order to gain migratory capacities. Such morphological changes have been first described during embryogenesis and are known to be under control of a series of transcription factors, some of which are also expressed during tumor progression. SNAIL1 factor (or SNAIL), whose role is determinant in many organogenesis steps, is also highly expressed at the invasive edge of several carcinoma and seems to participate in cancer cells dissemination. During the EMT process, SNAIL1 expression and localization, as well as its transcriptional activity, are under control of a complex regulation involving different post-translational modifications including phosphorylation. Therefore, the goal of my thesis was to understand regulation mechanisms of SNAIL1 by the protein-kinase CK2 in the context of EMT programs induction. This work was performed in two steps, of which the first was a biochemical characterisation of SNAIL1 phosphorylation by CK2 and its regulation by the CK2β regulatory subunit. In a second time, I focused on the consequences of CK2 inhibition by RNA interference in MCF10A mammary epithelial cells. This model highlighted the determining role of CK2β in maintaining epithelial phenotype and a cohesive architecture within MCF10A cells in vitro. Collectivelly, these findings suggest that protein- kinase CK2, under control of its regulatory subunit CK2β, acts as a negative regulator of SNAIL1 transcriptional level and protein stability in order to set against EMT induction.
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https://tel.archives-ouvertes.fr/tel-00568927
Contributor : Alexandre Deshiere <>
Submitted on : Saturday, October 1, 2011 - 7:00:05 AM
Last modification on : Wednesday, July 25, 2018 - 1:24:48 AM
Long-term archiving on : Monday, January 2, 2012 - 2:20:08 AM

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Alexandre Deshiere. Régulation du facteur de transcription SNAIL1 au cours de la Transition Epithélio-Mésenchymateuse dans les cellules mammaires MCF10A : implication de la protéine-kinase CK2. Biologie cellulaire. Université de Grenoble, 2010. Français. ⟨tel-00568927⟩

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