Publicação
Finding the mechanisms underlying cell intrinsic resistance to oncogenesis
| Resumo: | Susceptibility to oncogenic transformation depends not only on genetic alterations but also on the differentiation state of the target cells. In the eye epithelium of Drosophila melanogaster, differentiated cells respond to oncogenic stimuli with hyperplastic growth, whereas progenitor cells exhibit more restricted proliferation. To investigate this phenomenon, we hypothesized that progenitor cells possess intrinsic mechanisms that limit their responsiveness to mitogenic signals. Transcriptomic analysis of progenitor cells followed by a targeted genetic screen identified the progenitor Transcription Factor Optix as a candidate regulator of Yki-mediated growth. Manipulation of Optix produced distinct effects depending on both the region of the eye disc and the over-expression level: loss of function primarily compromised cell cycle arrest and the beginning of the differentiation process of progenitor cells, whereas overexpression in the differentiated domain, compromises cell cycle exit and results in altered epithelial architecture and neuronal differentiation patterns. We further examined the functional interaction between Optix and Yki, revealing a dose-dependent effect: ectopic expression at near-physiological levels suppressed Yki-induced hyperplasia in the differentiated domain, whereas higher levels enhanced tissue expansion and affects the differentiation of pigment cells. In silico structural modeling suggested the possibility of a direct interaction between Optix and Yki, and further assays using the Bantam reporter indicated that Optix might be a modulator of Yki transcriptional activity. These results identify Optix as a dose- and context-dependent modulator of Yki- mediated oncogenic signaling, highlighting how the nuclear landscape can determine susceptibility to oncogenic transformation. |
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| Autores principais: | Matos, Ana Beatriz Correia |
| Assunto: | Oncogenesis Cell differentiation Progenitor cells Optix Yorkie |
| Ano: | 2025 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso embargado |
| Instituição associada: | Universidade de Aveiro |
| Idioma: | inglês |
| Origem: | RIA - Repositório Institucional da Universidade de Aveiro |
| Resumo: | Susceptibility to oncogenic transformation depends not only on genetic alterations but also on the differentiation state of the target cells. In the eye epithelium of Drosophila melanogaster, differentiated cells respond to oncogenic stimuli with hyperplastic growth, whereas progenitor cells exhibit more restricted proliferation. To investigate this phenomenon, we hypothesized that progenitor cells possess intrinsic mechanisms that limit their responsiveness to mitogenic signals. Transcriptomic analysis of progenitor cells followed by a targeted genetic screen identified the progenitor Transcription Factor Optix as a candidate regulator of Yki-mediated growth. Manipulation of Optix produced distinct effects depending on both the region of the eye disc and the over-expression level: loss of function primarily compromised cell cycle arrest and the beginning of the differentiation process of progenitor cells, whereas overexpression in the differentiated domain, compromises cell cycle exit and results in altered epithelial architecture and neuronal differentiation patterns. We further examined the functional interaction between Optix and Yki, revealing a dose-dependent effect: ectopic expression at near-physiological levels suppressed Yki-induced hyperplasia in the differentiated domain, whereas higher levels enhanced tissue expansion and affects the differentiation of pigment cells. In silico structural modeling suggested the possibility of a direct interaction between Optix and Yki, and further assays using the Bantam reporter indicated that Optix might be a modulator of Yki transcriptional activity. These results identify Optix as a dose- and context-dependent modulator of Yki- mediated oncogenic signaling, highlighting how the nuclear landscape can determine susceptibility to oncogenic transformation. |
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