Wnt signaling modulates the response to DNA damage in the Drosophila wing imaginal disc by regulating the EGFR pathway DOI Creative Commons
Ben Ewen‐Campen, Norbert Perrimon

PLoS Biology, Journal Year: 2024, Volume and Issue: 22(7), P. e3002547 - e3002547

Published: July 24, 2024

Despite the deep conservation of DNA damage response (DDR) pathway, cells in different contexts vary widely their susceptibility to and propensity undergo apoptosis as a result genomic lesions. One cell signaling pathways implicated modulating DDR is highly conserved Wnt which known promote resistance caused by ionizing radiation variety human cancers. However, mechanisms linking signal transduction remain unclear. Here, we use genetically encoded system Drosophila reliably induce consistent levels vivo, demonstrate that canonical wing imaginal disc buffers against face double-strand breaks. We show Wg, primary ligand Drosophila, activates epidermal growth factor receptor (EGFR) via ligand-processing protease Rhomboid, which, turn, modulates Chk2-, p53-, E2F1-dependent manner. These studies provide mechanistic insight into modulation EGFR vivo proliferative tissue. Furthermore, they reveal how patterning functions are coupled with prosurvival, antiapoptotic activities, thereby facilitating developmental robustness damage.

Language: Английский

Studying Cellular Senescence Using the Model Organism Drosophila melanogaster DOI

Xanthippi P. Louka,

Sentiljana Gumeni, Ioannis P. Trougakos

et al.

Methods in molecular biology, Journal Year: 2025, Volume and Issue: unknown, P. 281 - 299

Published: Jan. 1, 2025

Language: Английский

Citations

0
Oncogenic signaling in the adult Drosophila prostate-like accessory gland leads to activation of a conserved pro-tumorigenic program, in the absence of proliferation. DOI Creative Commons

Samuel Jaimian Church,

Ajai J. Pulianmackal,

Joseph A. Dixon

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 12, 2024

Abstract Drosophila models for tumorigenesis and metastasis have revealed conserved mechanisms of signaling that are also involved in mammalian cancer. Many these use the proliferating tissues larval stages development, when highly mitotically active, or stem cells abundant. Fewer adult animals to initiate tumor formation many largely terminally differentiated postmitotic. The accessory glands prostate-like a model some aspects prostate using this tissue has been explored. In model, oncogenic was induced during proliferative stage gland raising question how activity would impact postmitotic tissue. Here, we show leads activation pro-tumorigenic program, similar observed mitotic tissues, but absence proliferation. Oncogenic hyperplasia with nuclear anaplasia aneuploidy through endoreduplication, which increases polyploidy occasionally results non-mitotic neoplastic-like extrusions. We compare gene expression changes our endocycling cancer by chemotherapy, potentially mediate recurrence after treatment. Similar pathways activated cells, suggesting provide useful progression do not involve cellular

Language: Английский

Citations

0
Wnt signaling modulates the response to DNA damage in the Drosophila wing imaginal disc by regulating the EGFR pathway DOI Creative Commons
Ben Ewen‐Campen, Norbert Perrimon

PLoS Biology, Journal Year: 2024, Volume and Issue: 22(7), P. e3002547 - e3002547

Published: July 24, 2024

Despite the deep conservation of DNA damage response (DDR) pathway, cells in different contexts vary widely their susceptibility to and propensity undergo apoptosis as a result genomic lesions. One cell signaling pathways implicated modulating DDR is highly conserved Wnt which known promote resistance caused by ionizing radiation variety human cancers. However, mechanisms linking signal transduction remain unclear. Here, we use genetically encoded system Drosophila reliably induce consistent levels vivo, demonstrate that canonical wing imaginal disc buffers against face double-strand breaks. We show Wg, primary ligand Drosophila, activates epidermal growth factor receptor (EGFR) via ligand-processing protease Rhomboid, which, turn, modulates Chk2-, p53-, E2F1-dependent manner. These studies provide mechanistic insight into modulation EGFR vivo proliferative tissue. Furthermore, they reveal how patterning functions are coupled with prosurvival, antiapoptotic activities, thereby facilitating developmental robustness damage.

Language: Английский

Citations

0