Estrogen receptor α promotes breast cancer by reprogramming cell metabolism [ChIP-seq]. Homo sapiens

Estrogen receptor α (ERα) is a key regulator of breast growth and breast cancer development. However, the role of ERα in metabolic reprogramming, a hallmark of cancer, is not well documented. In this study, using an integrated approach combining genome-wide mapping of chromatin bound ERα with estrogen induced transcript and metabolic profiling, we demonstrate that ERα reprograms metabolism upon estrogen stimulation, including changes in aerobic glycolysis, nucleotide and amino acid synthesis, and choline metabolism. We show, for the first time, that the ERα target gene choline phosphotransferase 1 (CHPT1) plays an essential role in estrogen induced increases in phosphatidylcholine (PtdCho) levels and that CHPT1 promotes tumorigenesis and proliferation. Furthermore, we show that CHPT1 is overexpressed in tumors compared to normal breast. We also demonstrate that ERα promotes aerobic glycolysis through increased expression of glycolytic genes. In conclusion, this study highlights the importance of ERα for metabolic alterations in breast cancer cells. Furthermore, overexpression of the ERα target CHPT1 in breast cancer supports its potential as a therapeutic target. Overall design: Examination of ERα DNA binding sites in T47D, a breast cancer cell line.