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<dc:title xml:lang="fr">Influence de l'élasticité du substrat sur la plasticité de la chromatine de cellules épithéliales et sur la division de cellules tumorales</dc:title>
<dcterms:alternative xml:lang="en">Influence of substrate elasticity on chromatic plasticity of epithelial cells and on division of tumoral cells</dcterms:alternative>
<dc:subject xml:lang="fr">Films multicouches de polyélectrolytes</dc:subject>
<dc:subject xml:lang="fr">Mécanobiologie</dc:subject>
<dc:subject xml:lang="fr">Élasticité du substrat</dc:subject>
<dc:subject xml:lang="fr">Division cellulaire</dc:subject>
<dc:subject xml:lang="fr">Instabilité chromosomique</dc:subject>
<dc:subject xml:lang="fr">Malignicité</dc:subject>
<dc:subject xml:lang="fr">Plasticité de la chromatine</dc:subject>
<dc:subject xml:lang="fr">Quiescence</dc:subject>
<dc:subject xml:lang="en">Polyelectrolytes multilayers films</dc:subject>
<dc:subject xml:lang="en">Mechanobiology</dc:subject>
<dc:subject xml:lang="en">Substrate elasticity</dc:subject>
<dc:subject xml:lang="en">Cell division</dc:subject>
<dc:subject xml:lang="en">Chromosome missegregation</dc:subject>
<dc:subject xml:lang="en">Malignancy</dc:subject>
<dc:subject xml:lang="en">Chromatin plasticity</dc:subject>
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<dcterms:abstract xml:lang="fr">Dans le domaine des biomatériaux, cette thèse s’intéresse à l’influence de l’élasticité du substrat sur la division et la plasticité de la chromatine de cellules épithéliales. La létalité des cellules est corrélée aux faibles rigidités des substrats. Cependant, quelques cellules tumorales SW480, incluant celles portant des anomalies de ségrégation des chromosomes, progressent en mitose. Ces anomalies seraient à l’origine de réarrangements chromosomiques, sources de nombreuses mutations. Les substrats mous conduisent à la formation d’hétérochromatine tandis que les substrats très mous induisent la nécrose des cellules PtK2. Sur ces substrats, l’euchromatine est maintenue après inhibition de HDAC, permettant aux cellules de résister à la nécrose, indépendamment de la compétence transcriptionnelle du noyau. Ces cellules s’étalent à nouveau après transfert sur un substrat rigide. Ces résultats suggèrent 1) une voie de signalisation entrante initiée par le substrat conduisant à la nécrose via la formation d’hétérochromatine 2) une voie de signalisation sortante initiée par l’euchromatine permettant la survie cellulaire.</dcterms:abstract>
<dcterms:abstract xml:lang="en">In the biomaterials field, this PhD work is about influence of substrate elasticity on cell division and chromatin plasticity of epithelial cells. Soft substrates cause massive death.However, some SW480 tumor cells, including those bearing chromosomal segregation abnormalities progress in mitosis. These abnormalities could result in more chromosomal rearrangements, increasing mutations. Soft substrates lead to heterochromatin remodelling and very soft substrates promote necrosis of PtK2 cells. On these substrates, euchromatin could be maintained after HDAC inhibition independently of the nuclear transcriptional competence.These cells spread again after tranfer on stiff substrates. These results suggest i) outside-insignalling cascade initiated at the soft substrate surface leading to heterochromatin remodelling and ultimately necrosis, ii) inside-out signaling cascade initiated from euchromatin allowing cell to overcome necrosis on soft substrate.</dcterms:abstract>
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