Publicação
Impact of centrosome amplification in the malignant transformation of Barrett’s esophagus
| Resumo: | Abstract Barrett's esophagus (BE) is a multistep premalignant condition, progressing from metaplasia, dysplasia, to, ultimately, esophageal adenocarcinoma (EAC).BE early detection, as well as stratifying its risk of progression, is becoming a growing concern. Centrosome amplification (CA) is observed in metaplastic BE cells and increases throughout progression, significantly increasing from metaplasia to dysplasia. Because CA has been described in many human cancers and may contribute to the development of malignancy, we hypothesized that CA may contribute to BE malignant progression by impacting the migration and invasion potentials of BE dysplastic cells. If this hypothesis is correct, a decrease of CA in dysplasia would be sufficient to reduce malignant properties such as invasiveness potential. Indeed, by depleting molecules of centriolar biogenesis to reduce the level of CA, we observed a reduced migratory and invasive potential of dysplastic cells. As epithelial-mesenchymal transition (EMT) is often linked to malignancy and invasion capacity, we investigated whether the reduction of extra centrosomes could result in an EMT reversal, increasing epithelial cellular traits and lessening mesenchymal features responsible for the migratory and invasive potential of the cells. Although the reduction of CA in dysplasia cells was not accompanied by significant changes in their EMT signature, there was a cytosolic accumulation of a component of the extracellular matrix. Notably, this was accompanied by reduced levels of this component in the extracellular space. In summary, our results indicate that CA contributes to the invasive potential in dysplasia and provides important clues into their mechanisms. This study provides new insights regarding the contribution of supernumerary centrosomes to the invasive potential in dysplasia, highlighting the importance of CA in the malignant progression of BE. These findings may contribute to the development of new biomarkers of progression and personalizing therapy. |
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| Autores principais: | Silveira, Bárbara Nunes de Amaral da Silva |
| Assunto: | Esófago de Barrett Amplificação de centrossomas Progressão tumoral Invasão Barrett´s esophagus Centrosome amplification Tumor progression Invasion |
| Ano: | 2024 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Instituto Politécnico de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório Científico do Instituto Politécnico de Lisboa |
| Resumo: | Abstract Barrett's esophagus (BE) is a multistep premalignant condition, progressing from metaplasia, dysplasia, to, ultimately, esophageal adenocarcinoma (EAC).BE early detection, as well as stratifying its risk of progression, is becoming a growing concern. Centrosome amplification (CA) is observed in metaplastic BE cells and increases throughout progression, significantly increasing from metaplasia to dysplasia. Because CA has been described in many human cancers and may contribute to the development of malignancy, we hypothesized that CA may contribute to BE malignant progression by impacting the migration and invasion potentials of BE dysplastic cells. If this hypothesis is correct, a decrease of CA in dysplasia would be sufficient to reduce malignant properties such as invasiveness potential. Indeed, by depleting molecules of centriolar biogenesis to reduce the level of CA, we observed a reduced migratory and invasive potential of dysplastic cells. As epithelial-mesenchymal transition (EMT) is often linked to malignancy and invasion capacity, we investigated whether the reduction of extra centrosomes could result in an EMT reversal, increasing epithelial cellular traits and lessening mesenchymal features responsible for the migratory and invasive potential of the cells. Although the reduction of CA in dysplasia cells was not accompanied by significant changes in their EMT signature, there was a cytosolic accumulation of a component of the extracellular matrix. Notably, this was accompanied by reduced levels of this component in the extracellular space. In summary, our results indicate that CA contributes to the invasive potential in dysplasia and provides important clues into their mechanisms. This study provides new insights regarding the contribution of supernumerary centrosomes to the invasive potential in dysplasia, highlighting the importance of CA in the malignant progression of BE. These findings may contribute to the development of new biomarkers of progression and personalizing therapy. |
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