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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RESEARCH ARTICLE|
05 May 2021
Aneuploidy facilitates dysplastic and tumorigenic phenotypes in the Drosophila gut
Rita Brás,
Rita Brás
1
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal
2
IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Portugal
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Augusta Monteiro
,
Augusta Monteiro
1
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal
2
IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Portugal
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Claudio E. Sunkel
,
Claudio E. Sunkel
*
1
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal
2
IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Portugal
3
ICBAS – Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Portugal
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Luís Pedro Resende
Luís Pedro Resende
*
1
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal
2
IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Portugal
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Rita Brás
1
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal
2
IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Portugal
Augusta Monteiro
1
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal
2
IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Portugal
Claudio E. Sunkel
*
1
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal
2
IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Portugal
3
ICBAS – Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Portugal
Luís Pedro Resende
*
1
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal
2
IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Portugal
Received:
02 Feb 2021
Accepted:
27 Apr 2021
© 2021. Published by The Company of Biologists Ltd
2021
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Biol Open bio.058623.
Article history
Received:
02 Feb 2021
Accepted:
27 Apr 2021
Currently Viewing Accepted Manuscript - Newer Version Available
03 Nov 2021
Citation
Rita Brás, Augusta Monteiro, Claudio E. Sunkel, Luís Pedro Resende; Aneuploidy facilitates dysplastic and tumorigenic phenotypes in the Drosophila gut. Biol Open 2021; bio.058623. doi: https://doi.org/10.1242/bio.058623
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