The NF-κB Pathway Promotes Tamoxifen Tolerance and Disease Recurrence in Estrogen Receptor-Positive Breast Cancers.

ABSTRACT: The purpose of this study was to identify critical pathways promoting survival of tamoxifen-tolerant, estrogen receptor α positive (ER⁺) breast cancer cells, which contribute to therapy resistance and disease recurrence. Gene expression profiling and pathway analysis were performed in ER⁺ breast tumors of patients before and after neoadjuvant tamoxifen treatment and demonstrated activation of the NF-κB pathway and an enrichment of epithelial-to mesenchymal transition (EMT)/stemness features. Exposure of ER⁺ breast cancer cell lines to tamoxifen, in vitro and in vivo, gives rise to a tamoxifen-tolerant population with similar NF-κB activity and EMT/stemness characteristics. Small-molecule inhibitors and CRISPR/Cas9 knockout were used to assess

SUBMITTER: Kastrati I 

PROVIDER: S-EPMC7335344 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature