What makes a cell responsive to oncogenes?

• Autor(a) principal: Castro, Laura de Jesus Jorge Oliveira de
• Data de Publicação: 2022
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/34356
• topic: Oncogenic signals; Pioneer factors; Chromatin remodelers; Grainy head; Yorkie

A puzzling feature of cancer development is that distinct cell populations, within a tissue, can respond differently to similar oncogenic signals. This suggests that the mechanisms underlying oncogenic susceptibility may vary between cell types/states. In the Drosophila melanogaster eye imaginal disc, cells in an advanced stage of differentiation are more proliferative in response to oncogenic stimuli than the “naïve” progenitor cells from which they derived. Our goal is to understand what makes a cell responsive to oncogenic signals, using as a model the overexpression of the constitutively active oncogene Yki. Our hypothesis is that the pioneer factor Grh works together with chromatin remodelers to make cells responsive to the activation of the Yki oncogene. To explore how chromatin modulations mediate the oncogenic stimuli response, we used available tools to modulate Grh expression and deplete different chromatin remodelers. We observed that Grh and some chromatin remodelers can modulate de response to oncogenic signals because they showed strong synergy with Yki-induced overgrowth. These indicate that chromatin status is critical for the correct interpretation of oncogenic signals. Additionally, Grh expression levels must be controlled regardless of the cell differentiation state. In the case of modeling by chromatin remodelers, their requirement is distinguished according to the state of cell differentiation. Our data indicate that PcG is more associated with the repression of genes associated with proliferation and, on the other hand, TrxG is more associated with allowing cell differentiation. Grh is necessary, first for proliferation, and later, it becomes essential for differentiation.