EXO1 overexpression induces homologous recombination deficiency and enhances PARP inhibitor sensitivity in ER-positive breast cancer: modulation by N4BP2L2-Mediated restoration.

ABSTRACT: Exonuclease 1 (EXO1) is a critical enzyme in homologous recombination (HR) and is implicated in cancer progression, with overexpression linked to poor prognosis in multiple tumor types. Yet, the impact of EXO1 overexpression on HR efficiency in estrogen receptor (ER)-positive breast cancer remains unclear. Here, we investigated this using The Cancer Genome Atlas (TCGA) and functional studies in ER-positive T47D cells. High EXO1 expression was associated with elevated homologous recombination deficiency (HRD) scores in ER-positive tumors, indicating impaired HR activity. In T47D cells, EXO1 overexpression reduced HR efficiency, measured by the Advanced Homologous Recombination Assay (ASHRA), and increased sensitivity to the PARP inhibitor olaparib. Using multi-cohort transcriptomic analysis

SUBMITTER: Sugiyama R 

PROVIDER: S-EPMC12660296 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature