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• W4377019638 abstract "ABSTRACT Cellular senescence is a conserved biological process essential for embryonic development, tissue remodeling, repair, and a key regulator of aging. Senescence also plays a crucial role in cancer, though this role can be tumor-suppressive or tumor-promoting, depending on the genetic context and the microenvironment. The highly heterogeneous, dynamic, and context-dependent nature of senescence-associated features and the relatively small numbers of senescent cells in tissues makes in vivo mechanistic studies of senescence challenging. As a result, which senescence-associated features are observed in which disease contexts and how they contribute to disease phenotypes remain largely unknown. Similarly, the specific mechanisms by which various senescence-inducing signals are integrated in vivo to induce senescence and why some cells become senescent while their immediate neighbors do not are unclear. Here, we identify a small number of cells that exhibit multiple features of senescence in a genetically complex model of intestinal transformation we recently established in the developing Drosophila larval hindgut epithelium. We demonstrate that these cells emerge in response to concurrent activation of AKT, JNK, and DNA damage response pathways within transformed tissue. Eliminating senescent cells, genetically or by treatment with senolytic compounds, reduces overgrowth and improves survival. We find that this tumor-promoting role is mediated by Drosophila macrophages recruited to the transformed tissue by senescent cells, which results in non-autonomous activation of JNK signaling within the transformed epithelium. These findings emphasize complex cell-cell interactions underlying epithelial transformation and identify senescent cell-macrophage interactions as a potential druggable node in cancer. One sentence summary: Interactions between transformed senescent cells and macrophages drive tumorigenesis." @default.
• W4377019638 created "2023-05-19" @default.
• W4377019638 creator A5015524604 @default.
• W4377019638 creator A5019105041 @default.
• W4377019638 date "2023-05-18" @default.
• W4377019638 modified "2023-10-17" @default.
• W4377019638 title "Senescent cells and macrophages cooperate through a multi-kinase signaling network to promote intestinal transformation in Drosophila" @default.
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• W4377019638 doi "https://doi.org/10.1101/2023.05.15.540869" @default.
• W4377019638 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37292988" @default.
• W4377019638 hasPublicationYear "2023" @default.
• W4377019638 type Work @default.
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• W4377019638 hasAuthorship W4377019638A5015524604 @default.

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