Chromosomal instability-induced cell invasion through caspase-driven DNA damage
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...
| Autores: | , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/203359 |
| Acceso en línea: | https://hdl.handle.net/2445/203359 |
| Access Level: | acceso abierto |
| Palabra clave: | Mitosi Anomalies cromosòmiques Mitosis Chromosome abnormalities |
| Sumario: | 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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