Aneuploidy facilitates dysplastic and tumorigenic phenotypes in the Drosophila gut

Detalhes bibliográficos
Autor(a) principal: Brás, R
Data de Publicação: 2021
Outros Autores: Monteiro, A, Sunkel, CE, Resende, LP
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: https://hdl.handle.net/10216/155836
Resumo: Aneuploidy has been strongly linked to cancer development, and published evidence has suggested that aneuploidy can have an oncogenic or a tumor suppressor role depending on the tissue context. Using the Drosophila midgut as a model, we have recently described that adult intestinal stem cells (ISCs), do not activate programmed cell death upon aneuploidy induction, leading to an increase in ISC proliferation rate, and tissue dysplasia. How aneuploidy impacts ISCs in intestinal tumorigenic models remains to be investigated, and it represents a very important biological question to address since data from multiple in vivo models suggests that the cellular impact of aneuploidy is highly dependent on the cellular and tissue context. Using manipulation of different genetic pathways such as EGFR, JAK-STAT and Notch that cause dysplastic phenotypes in the Drosophila gut, we found that concomitant aneuploidy induction by impairment of the Spindle Assembly Checkpoint (SAC) consistently leads to a more severe progression of intestinal dysplasia or tumorigenesis. This is characterized by an accumulation of progenitor cells, high tissue cell density and higher stem cell proliferation rates, revealing an additive or synergistic effect depending on the misregulated pathway in which aneuploidy was induced. Thus, our data suggests that in the Drosophila gut, both dysplasia and tumorigenic phenotypes can be fueled by inducing genomic instability of resident stem cells.
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spelling Aneuploidy facilitates dysplastic and tumorigenic phenotypes in the Drosophila gutAneuploidyCancerMitosisSpindle-assembly checkpointStem cellsAneuploidy has been strongly linked to cancer development, and published evidence has suggested that aneuploidy can have an oncogenic or a tumor suppressor role depending on the tissue context. Using the Drosophila midgut as a model, we have recently described that adult intestinal stem cells (ISCs), do not activate programmed cell death upon aneuploidy induction, leading to an increase in ISC proliferation rate, and tissue dysplasia. How aneuploidy impacts ISCs in intestinal tumorigenic models remains to be investigated, and it represents a very important biological question to address since data from multiple in vivo models suggests that the cellular impact of aneuploidy is highly dependent on the cellular and tissue context. Using manipulation of different genetic pathways such as EGFR, JAK-STAT and Notch that cause dysplastic phenotypes in the Drosophila gut, we found that concomitant aneuploidy induction by impairment of the Spindle Assembly Checkpoint (SAC) consistently leads to a more severe progression of intestinal dysplasia or tumorigenesis. This is characterized by an accumulation of progenitor cells, high tissue cell density and higher stem cell proliferation rates, revealing an additive or synergistic effect depending on the misregulated pathway in which aneuploidy was induced. Thus, our data suggests that in the Drosophila gut, both dysplasia and tumorigenic phenotypes can be fueled by inducing genomic instability of resident stem cells.Company of Biologists20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10216/155836eng2046-639010.1242/bio.058623Brás, RMonteiro, ASunkel, CEResende, LPinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-12-22T01:35:45Zoai:repositorio-aberto.up.pt:10216/155836Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:54:32.850837Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Aneuploidy facilitates dysplastic and tumorigenic phenotypes in the Drosophila gut
title Aneuploidy facilitates dysplastic and tumorigenic phenotypes in the Drosophila gut
spellingShingle Aneuploidy facilitates dysplastic and tumorigenic phenotypes in the Drosophila gut
Brás, R
Aneuploidy
Cancer
Mitosis
Spindle-assembly checkpoint
Stem cells
title_short Aneuploidy facilitates dysplastic and tumorigenic phenotypes in the Drosophila gut
title_full Aneuploidy facilitates dysplastic and tumorigenic phenotypes in the Drosophila gut
title_fullStr Aneuploidy facilitates dysplastic and tumorigenic phenotypes in the Drosophila gut
title_full_unstemmed Aneuploidy facilitates dysplastic and tumorigenic phenotypes in the Drosophila gut
title_sort Aneuploidy facilitates dysplastic and tumorigenic phenotypes in the Drosophila gut
author Brás, R
author_facet Brás, R
Monteiro, A
Sunkel, CE
Resende, LP
author_role author
author2 Monteiro, A
Sunkel, CE
Resende, LP
author2_role author
author
author
dc.contributor.author.fl_str_mv Brás, R
Monteiro, A
Sunkel, CE
Resende, LP
dc.subject.por.fl_str_mv Aneuploidy
Cancer
Mitosis
Spindle-assembly checkpoint
Stem cells
topic Aneuploidy
Cancer
Mitosis
Spindle-assembly checkpoint
Stem cells
description Aneuploidy has been strongly linked to cancer development, and published evidence has suggested that aneuploidy can have an oncogenic or a tumor suppressor role depending on the tissue context. Using the Drosophila midgut as a model, we have recently described that adult intestinal stem cells (ISCs), do not activate programmed cell death upon aneuploidy induction, leading to an increase in ISC proliferation rate, and tissue dysplasia. How aneuploidy impacts ISCs in intestinal tumorigenic models remains to be investigated, and it represents a very important biological question to address since data from multiple in vivo models suggests that the cellular impact of aneuploidy is highly dependent on the cellular and tissue context. Using manipulation of different genetic pathways such as EGFR, JAK-STAT and Notch that cause dysplastic phenotypes in the Drosophila gut, we found that concomitant aneuploidy induction by impairment of the Spindle Assembly Checkpoint (SAC) consistently leads to a more severe progression of intestinal dysplasia or tumorigenesis. This is characterized by an accumulation of progenitor cells, high tissue cell density and higher stem cell proliferation rates, revealing an additive or synergistic effect depending on the misregulated pathway in which aneuploidy was induced. Thus, our data suggests that in the Drosophila gut, both dysplasia and tumorigenic phenotypes can be fueled by inducing genomic instability of resident stem cells.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://hdl.handle.net/10216/155836
url https://hdl.handle.net/10216/155836
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2046-6390
10.1242/bio.058623
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dc.publisher.none.fl_str_mv Company of Biologists
publisher.none.fl_str_mv Company of Biologists
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instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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