Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/203359
Title: | Chromosomal instability-induced cell invasion through caspase-driven DNA damage |
Author: | Barrio, Lara Gaspar, Ana Elena Muzzopappa, Mariana Ghosh, Kaustuv Romão, Daniela Clemente Ruiz, Marta Milán, Marco |
Keywords: | Mitosi Anomalies cromosòmiques Mitosis Chromosome abnormalities |
Issue Date: | 25-Sep-2023 |
Publisher: | Elsevier |
Abstract: | Chromosomal instability (CIN), an increased rate of changes in chromosome structure and number, is observed in most sporadic human carcinomas with high metastatic activity. Here, we use a Drosophila epithelial model to show that DNA damage, as a result of the production of lagging chromosomes during mitosis and aneuploidy-induced replicative stress, contributes to CIN-induced invasiveness. We unravel a sub-lethal role of effector caspases in invasiveness by enhancing CIN-induced DNA damage and identify the JAK/STAT signaling pathway as an activator of apoptotic caspases through transcriptional induction of pro-apoptotic genes. We provide evidence that an autocrine feedforward amplification loop mediated by Upd3-a cytokine with homology to interleukin-6 and a ligand of the JAK/STAT signaling pathway-contributes to amplifying the activation levels of the apoptotic pathway in migrating cells, thus promoting CIN-induced invasiveness. This work sheds new light on the chromosome-signature-independent effects of CIN in metastasis.Copyright © 2023 Elsevier Inc. All rights reserved. |
Note: | Reproducció del document publicat a: https://doi.org/10.1016/j.cub.2023.09.004 |
It is part of: | Current Biology, 2023, vol. 33, num. 20, p. 4446-4457 |
URI: | http://hdl.handle.net/2445/203359 |
Related resource: | https://doi.org/10.1016/j.cub.2023.09.004 |
ISSN: | 1879-0445 |
Appears in Collections: | Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona)) |
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