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.
Aneuploidy facilitates dysplastic and tumorigenic phenotypes in the Drosophila gut
Currently Viewing Accepted Manuscript - Newer Version Available
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
Download citation file:
Advertisement
Read & Publish Open Access publishing: what authors say
We have had great feedback from authors who have benefitted from our Read & Publish agreement with their institution and have been able to publish Open Access with us without paying an APC. Read what they had to say.
Gatekeeping at BiO
In his Editorial, BiO Editor-in-Chief Dan Gorelick outlines the criteria by which articles submitted to BiO are assessed, as part of initiatives to increase transparency of journal 'gatekeeping'.
The Forest of Biologists
Our Publisher Claire Moulton recently visited the two Woodland Trust UK sites where we are planting new native trees for published Research and Review papers and protecting ancient woodland on behalf of our peer reviewers.
A Year at the Forefront
This series of Review articles aims to highlight the key discoveries, technological innovations, new resources and new hypotheses that have made an impact in a specific biological field during the past year. This publishing opportunity is available to early-career researchers, without a publication charge. Find out about eligibility and how to submit a proposal.
How we support early-career researchers
Biology Open, its sister journals and its not-for-profit publisher, The Company of Biologists, support early-career researchers in numerous ways, helping them grow their network and raise their profile. Find out what we can do to support you.