GSE204667
Determination of the genome wide binding pattern of TLE3 in luminal breast cancer
The identification of mechanisms controlling breast tumor progression from less aggressive to highly metastatic disease should provide novel therapeutic targets for patients. Here we report the transcriptional corepressor, TLE3, as a critical regulator of cellular plasticity in breast cancer. TLE3 facilitates repression of genes associated with the highly aggressive basal-like breast cancer (BLBC) subtype within luminal cells. Additionally, maintenance of the luminal lineage is dependent on appropriate localization of TLE3 to its transcriptional targets which is mediated through interaction with FOXA1. Furthermore, the ability of TLE3 to repress BLBC transcription results in reduced metastatic capacity and aggressive cellular behaviors. Together our findings establish TLE3 as a critical transcriptional mediator of breast cancer aggressiveness, with TLE3 sustaining the more differentiated and less metastatic nature of luminal tumors through suppression of gene expression programs associated with BLBC. Overall design: We performed Chip-seq to determine genome wide binding pattens of TLE3 in the luminal breast cancer cell lines, MDA-MB-453. SKBR3, and T47D. Additionally, we performed ChIP-seq for the transcription factor, FOXA1 in these cell lines and determine the extent of TLE3/FOXA1 co-binding in luminal breast cancer.