HRK downregulation and augmented BCL-xL binding to BAK confer apoptotic protection to therapy-induced senescent melanoma cells.

ABSTRACT: Senescent cells are commonly detected in tumors after chemo and radiotherapy, leading to a characteristic cellular phenotype that resists apoptotic cell death. In this study, we used multiple melanoma cell lines, molecular markers, and therapies to investigate the key role of the BCL-2 family proteins in the survival of senescent cells. We first used BH3 profiling to assess changes in apoptotic priming upon senescence induction. Unexpectedly, not all cell types analyzed showed a decrease in apoptotic priming, BIM was downregulated, there was variability in BAX expression and BAK remained constant or increased. Therefore, there was not a clear pattern for pro-survival adaptation. Many studies have been devoted to find ways to eliminate senescent cells, leading to one of the most studied sen

SUBMITTER: Alcon C 

PROVIDER: S-EPMC11982230 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature