Dissecting cellular senescence and SASP in Drosophila

Takao Ito, Tatsushi Igaki

Cellular senescence can act as both tumor suppressor and tumor promoter depending on the cellular contexts. On one hand, premature senescence has been considered as an innate host defense mechanism against carcinogenesis in mammals. In response to various stresses including oxidative stress, DNA damage, and oncogenic stress, suffered cells undergo irreversible cell cycle arrest, leading to tumor suppression. On the other hand, recent studies in mammalian systems have revealed that senescent cells can drive oncogenesis by secreting diverse proteins such as inflammatory cytokines, matrix remodeling factors, and growth factors, the phenomenon called senescence-associated secretory phenotype (SASP). However, the mechanisms by which these contradictory effects regulate tumor growth and metastasis in vivo have been elusive. Here, we review the recent discovery of cellular senescence in Drosophila and the mechanisms underlying senescence-mediated tumor regulation dissected by Drosophila genetics.