Impaired Cdc20 signaling promotes senescence in normal cells and apoptosis in non-small cell lung cancer cells.

ABSTRACT: Cellular senescence is a form of irreversible growth arrest that cancer cells evade. The cell division cycle protein 20 homolog (Cdc20) is a positive regulator of cell division, but how its dysregulation may relate to senescence is unclear. Here, we find that Cdc20 mRNA and protein expression are downregulated in stress-induced premature senescent lung fibroblasts in a p53-dependent manner. Either Cdc20 downregulation or inhibition of anaphase-promoting complex/cyclosome (APC/C) is sufficient to induce premature senescence in lung fibroblasts, while APC/C activation inhibits stress-induced premature senescence. Mechanistically, we show both Cdc20 downregulation and APC/C inhibition induce premature senescence through glycogen synthase kinase (GSK)-3β-mediated phosphorylation and downregula

SUBMITTER: Volonte D 

PROVIDER: S-EPMC9490043 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature