RT Journal Article SR Electronic T1 Lack of apoptosis leads to cellular senescence and tumorigenesis in Drosophila epithelial cells JF bioRxiv FD Cold Spring Harbor Laboratory SP 2023.05.08.539867 DO 10.1101/2023.05.08.539867 A1 Juan Manuel Garcia-Arias A1 Noelia Pinal A1 Sara Cristóbal Vargas A1 Carlos Estella A1 Ginés Morata YR 2023 UL http://biorxiv.org/content/early/2023/05/21/2023.05.08.539867.abstract AB Programmed cell death (apoptosis) is a homeostasis program of animal tissues designed to remove cells that are unwanted or are damaged by physiological insults. To assess the functional role of apoptosis we have studied the consequences of subjecting Drosophila epithelial cells defective in apoptosis to stress or genetic perturbations that normally cause massive cell death. We find that many of those cells acquire persistent activity of the JNK pathway, which drives them into senescent status, characterized by arrest of cell division, cell hypertrophy, Senescent Associated ß-gal activity (SA-ß-gal), ROS production, Senescent Associated Secretory Phenotype (SASP) and migratory behaviour. We have identified two classes of senescent cells in the wing disc: 1) those that localize to the appendage part of the disc, express the upd, wg and dpp signalling genes and generate tumour overgrowths, and 2) those located in the thoracic region do not express wg and dpp nor they induce tumour overgrowths. Whether to become tumorigenic or non-tumorigenic depends on the original identity of the cell prior to the transformation. We also find that the p53 gene contributes to senescence by enhancing the activity of JNK.Competing Interest StatementThe authors have declared no competing interest.