Oncogenic signaling in the Drosophila prostate-like accessory gland activates a pro-tumorigenic program in the absence of proliferation

Disease Models & Mechanisms, Journal Year: 2025, Volume and Issue: 18(4)

Published: April 1, 2025

ABSTRACT Drosophila models for tumorigenesis have revealed conserved mechanisms of signaling involved in mammalian cancer. Many these use highly mitotically active tissues. Few adult tissues, when most cells are terminally differentiated and postmitotic. The accessory glands prostate-like a model prostate using this tissue has been explored. In prior model, oncogenic was induced during the proliferative stages gland development, raising question how activity impacts differentiated, postmitotic tissue. Here, we show that leads to activation pro-tumorigenic program, similar mitotic but absence proliferation. our experiments, led hypertrophy with nuclear anaplasia, part through endoreduplication. Oncogene-induced gene expression changes overlapped those polyploid cancer after chemotherapy, which potentially mediate tumor recurrence. Thus, provide useful aspects progression lack cellular

Language: Английский

Hippo-TOR Signaling Crosstalks Underpin Microtubule Acetylation-linked Carcinogenesis inDrosophilaSquamous Epithelia

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

Published: Aug. 9, 2024

ABSTRACT Flattened squamous epithelial tissues undergo extensive cytoskeletal remodeling and display perpetual nuclear signaling of the Hippo transcription cofactor, YAP/TAZ, in mammals Yki Drosophila . Loss YAP humans or causes cell carcinoma (SCC), but only select types. Here, we reveal a mechanism Yki-loss induced SCC lumen-lining epithelium male accessory gland (MAG) loss MAG triggers TOR signaling-mediated microtubule hyperacetylation, which causally underpins its SCC. By contrast, oocyte-enveloping follicular neither activates nor induce hyperacetylation. Analysis available single-cell transcriptomic data further revealed characteristic type-specific signatures signaling. Thus, disparate epigenetic landscapes distinct mechanosensory cues likely prefigures their susceptibility to Yki-loss, with epithelia being oncogenically more susceptible.

Language: Английский