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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/203359
Chromosomal instability-induced cell invasion through caspase-driven DNA damage
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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.
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BARRIO, Lara, GASPAR, Ana elena, MUZZOPAPPA, Mariana, GHOSH, Kaustuv, ROMÃO, Daniela, CLEMENTE RUIZ, Marta, MILÁN, Marco. Chromosomal instability-induced cell invasion through caspase-driven DNA damage. _Current Biology_. 2023. Vol. 33, núm. 20, pàgs. 4446-4457. [consulta: 21 de gener de 2026]. ISSN: 1879-0445. [Disponible a: https://hdl.handle.net/2445/203359]