The transcriptome of highly aneuploid senescent cells reveals interaction with the tumor microenvironment and a pro-survival role of Yorkie

Drosophila epithelial tumor models have been instrumental in demonstrating that, beyond the generation of genomic copy number heterogeneity, CIN can act as a source of tumor growth, metastasis and malignancy through the production of aneuploidy-induced senescent cells. Here we characterized the transcriptional program of these cells.

We present evidence that most cellular responses to aneuploidy and senescence, such as cell cycle arrest, autophagy induction, activation of the actin cytoskeleton and upregulation of genes involved in secretion, are reflected at the transcriptional level. Besides those secreted proteins mediating tumor growth, metastasis and malignancy, we unravel a role of Upd1 cytokine in driving the death of the nearby tumor microenvironment through activation of the JAK/STAT pathway and induction of autophagy.