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Understanding how capping of actin filaments prevents epithelium to mesenchymal like transitions in genetically defined epithelial tissues
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Resumo(s)
The actin cytoskeleton has a central role in controlling cell shape and mobility. In epithelia, a circumferential band of actin filaments provides the structural support for cell-cell junctions. When the strength of the epithelium is compromised, cells may undergo epithelium to mesenchymal transition, escape size-control mechanisms, evade cell death and finally acquire the ability to migrate. These features recapitulate all of the hallmarks that characterize cancer malignancy. Interestingly, clones of cells mutant for either subunits of the capping protein ab heterodimer (CP), induced in a heterozygous wild-type background, are extruded from the wing blade epithelium and die. However, depleting the subunit (cpb) by RNA interference (RNAi) in the whole blade leads to a different outcome: epithelium polarity is strongly affected, few apoptotic cells can be observed, while many seem to overproliferate. This differential behavior is unlikely to be due to a dosage effect since RNAi induced-cpb depletion in restricted wing blade domains also induces cell extrusion and death. This suggests that CP prevents tumorigenesis of wing blade cells. However, when CP mutant cells are adjacent to wildtype wing blade neighboring cells, the latest eliminate mutant cells by a process of cell competition. The role of CP in preventing tumorigenesis might be related to its major function, preventing excessive actin polimerization, or to additional functions, such as the maintenance of epithelial cell polarity. The tumor suppressor function of CP appears to be tissue specific since the above cell behavior is only observed in restricted epithelia. This suggests that each epithelium has specific cytoskeleton and/or junctional properties, making cells sensitive or not to mutations that cause abnormal tumor growth. Altogether the presented data highlight the crucial impact of tissue context for the activation of a tumoral process
Resumo alargado em português disponível no documento
Resumo alargado em português disponível no documento
Descrição
Tese de mestrado, Biologia (Biologia Evolutiva e do Desenvolvimento), 2007, Universidade de Lisboa, Faculdade de Ciências
Palavras-chave
Biologia celular Apoptose Células epiteliais Teses de mestrado