BCL-3 loss sensitises colorectal cancer cells to DNA damage by targeting homologous recombination.

ABSTRACT: The proto-oncogene BCL-3 is upregulated in a subset of colorectal cancers (CRC), where it has been shown to enhance tumour cell survival. However, although increased expression correlates with poor patient prognosis, the role of BCL-3 in determining therapeutic response remains largely unknown. In this study, we use combined approaches in multiple cell lines and pre-clinical mouse models to investigate the function of BCL-3 in the DNA damage response. We show that suppression of BCL-3 increases γH2AX foci formation and decreases homologous recombination in CRC cells, resulting in reduced RAD51 foci number and increased sensitivity to PARP inhibition. Importantly, a similar phenotype is seen in Bcl3^-/- mice, where Bcl3^-/- mouse crypts also exhibit sensitivity to DNA da

SUBMITTER: Parker C 

PROVIDER: S-EPMC10618080 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature