Beyond the Passenger Seat: Survivin in the Transition from Proliferation to Senescence

Survivin (BIRC5), a core component of the chromosomal passenger complex (CPC), is essential for faithful mitosis and frequently overexpressed in human cancers. Despite extensive investigation of its mitotic and cell survival functions, its relationship with cellular senescence remains poorly understood. We investigated Survivin in therapy- and stress-induced senescence models and examined the consequences of transient Survivin depletion by RNA interference. Camptothecin treatment of HCT116 wt and A549 cells and oxidative stress in WI-38 fibroblasts induced characteristic morphological changes, increased senescence-associated β-galactosidase activity and reduced DNA synthesis. In HCT116 wt and A549 cells, senescence induction was accompanied by changes in cell-cycle regulatory proteins and altered immunofluorescence patterns of cell-cycle and chromatin-associated proteins. Survivin-targeting siRNA promoted pronounced senescence-associated morphological changes and increased β-galactosidase activity in HCT116 wt cells, whereas A549 cells exhibited a less pronounced response. These phenotypic differences were accompanied by changes in p53, p21 and CDK1 protein levels during the observation period. However, transient Survivin depletion does not establish whether the observed changes represent stable or irreversible senescence. Together, our findings support a cell-context-dependent association between Survivin perturbation and senescence-associated phenotypes, extending its biological significance beyond mitosis and highlighting cellular senescence as a potential outcome relevant to Survivin-targeted anticancer strategies.