生物
细胞生物学
果蝇属(亚属)
转化(遗传学)
信号转导
巨噬细胞
激酶
基因
遗传学
体外
作者
Ishwaree Datta,Erdem Bangi
标识
DOI:10.1016/j.devcel.2024.01.009
摘要
Cellular senescence is a conserved biological process that plays a crucial and context-dependent role in cancer. The highly heterogeneous and dynamic nature of senescent cells and their small numbers in tissues make in vivo mechanistic studies of senescence challenging. As a result, how multiple senescence-inducing signals are integrated in vivo to drive senescence in only a small number of cells is unclear. Here, we identify cells that exhibit multiple features of senescence in a Drosophila model of intestinal transformation, which emerge in response to concurrent activation of AKT, JNK, and DNA damage signaling within transformed tissue. Eliminating senescent cells, genetically or by treatment with senolytic compounds, reduces overgrowth and improves survival. We find that senescent cells promote tumorigenesis by recruiting Drosophila macrophages to the transformed tissue, which results in non-autonomous activation of JNK signaling. These findings identify senescent cell-macrophage interactions as an important driver of epithelial transformation.
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