Aneuploidy facilitates dysplastic and tumorigenic phenotypes in the Drosophila gut

• Type: Article in International Scientific Journal
• Date: 2021

Authors

Bras, R (Author) Other; Monteiro, A (Author) Other; Sunkel, CE (Author) ICBAS; Resende, LP (Author) Other

Journal

Title: Biology Open

Vol. 10

Publisher: The Company of Biologists Ltd.

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 0 Citations

Other information

Authenticus ID: P-00V-TMT

DOI: 10.1242/bio.058623

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8