Lack of apoptosis leads to cellular senescence and tumorigenesis inDrosophilaepithelial cells

Abstract

SummaryProgrammed 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 subjectingDrosophilaepithelial 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 theupd,wganddppsignalling genes and generate tumour overgrowths, and 2) those located in the thoracic region do not expresswganddppnor 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 thep53gene contributes to senescence by enhancing the activity of JNK.