PT  - JOURNAL ARTICLE
AU  - Juan Manuel Garcia-Arias
AU  - Noelia Pinal
AU  - Sara Cristóbal Vargas
AU  - Carlos Estella
AU  - Ginés Morata
TI  - Lack of apoptosis leads to cellular senescence and tumorigenesis in <em>Drosophila</em> epithelial cells
AID  - 10.1101/2023.05.08.539867
DP  - 2023 Jan 01
TA  - bioRxiv
PG  - 2023.05.08.539867
4099  - http://biorxiv.org/content/early/2023/05/21/2023.05.08.539867.short
4100  - http://biorxiv.org/content/early/2023/05/21/2023.05.08.539867.full
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.