Estrogen receptor a promotes breast cancer by reprogramming cell metabolism [ChIP-seq]

Estrogen receptor a (ERa) is a key regulator of breast growth and breast cancer development. However, the role of ERa 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 ERa with estrogen induced transcript and metabolic profiling, we demonstrate that ERa 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 ERa 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 ERa promotes aerobic glycolysis through increased expression of glycolytic genes. In conclusion, this study highlights the importance of ERa for metabolic alterations in breast cancer cells. Furthermore, overexpression of the ERa target CHPT1 in breast cancer supports its potential as a therapeutic target. Overall design: Examination of ERa DNA binding sites in T47D, a breast cancer cell line.