The Megacomplex protects ER-alpha from degradation by Fulvestrant in epithelial ovarian cancer.

ABSTRACT: Ovarian cancer, a significant contributor to cancer-related mortality, exhibits limited responsiveness to hormonal therapies targeting the estrogen receptor (ERα). This study aimed to elucidate the mechanisms behind ERα resistance to the therapeutic drug Fulvestrant (ICI182780 or ICI). Notably, compared to the cytoplasmic version, nuclear ERα was minimally degraded by ICI, suggesting a mechanism for drug resistance via the protective confines of the nuclear substructures. Of these substructures, we identified a 1.3 MDa Megacomplex comprising transcription factors ERα, FOXA1, and PITX1 using size exclusion chromatography (SEC) in the ovarian cancer cell line, PEO4. ChIP-seq revealed these factors colocalized at 6775 genomic positions representing sites of Megacomplex formation. Megacomplex

SUBMITTER: Jaiswal SK 

PROVIDER: S-EPMC12276986 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature