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

Autor:	Church SJ; Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI., Pulianmackal AJ; Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI., Dixon JA; Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI., Loftus LV; Cancer Ecology Center, The Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD., Amend SR; Cancer Ecology Center, The Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD., Pienta K; Cancer Ecology Center, The Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD., Cackowski FC; Karmanos Cancer Institute and Wayne State University Department of Oncology, Detroit, MI., Buttitta LA; Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Jun 07. Date of Electronic Publication: 2024 Jun 07.
DOI:	10.1101/2024.05.10.593549
Abstrakt:	Drosophila models for tumorigenesis and metastasis have revealed conserved mechanisms of signaling that are also involved in mammalian cancer. Many of these models use the proliferating tissues of the larval stages of Drosophila development, when tissues are highly mitotically active, or stem cells are abundant. Fewer Drosophila tumorigenesis models use adult animals to initiate tumor formation when many tissues are largely terminally differentiated and postmitotic. The Drosophila accessory glands are prostate-like tissues and a model for some aspects of prostate tumorigenesis using this tissue has been explored. In this model, oncogenic signaling was induced during the proliferative stage of accessory gland development, raising the question of how oncogenic activity would impact the terminally differentiated and postmitotic adult tissue. Here, we show that oncogenic signaling in the adult Drosophila accessory gland leads to activation of a conserved pro-tumorigenic program, similar to that observed in mitotic larval tissues, but in the absence of proliferation. Oncogenic signaling in the adult postmitotic gland leads to tissue hyperplasia with nuclear anaplasia and aneuploidy through endoreduplication, which increases polyploidy and occasionally results in non-mitotic neoplastic-like extrusions. We compare gene expression changes in our Drosophila model with that of endocycling prostate cancer cells induced by chemotherapy, which potentially mediate tumor recurrence after treatment. Similar signaling pathways are activated in the Drosophila gland and endocycling cancer cells, suggesting the adult accessory glands provide a useful model for aspects of prostate cancer progression that do not involve cellular proliferation. Competing Interests: Conflicts of Interest: Kenneth Pienta discloses that he is a consultant to Cue Biopharma Inc., an equity holder in PEEL therapeutics, an equity holder in Keystone Biopharma Inc, and an equity holder in Kreftect, Inc. Sarah Amend discloses that she is an equity holder in Keystone Biopharma Inc.
Databáze:	MEDLINE
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