ZFIN ID: ZDB-PUB-160728-16
Estrogen receptor α promotes breast cancer by reprogramming choline metabolism
Jia, M., Andreassen, T., Jensen, L., Bathen, T.F., Sinha, I., Gao, H., Zhao, C., Haldosén, L.A., Cao, Y., Girnita, L., Moestue, S.A., Dahlman-Wright, K.
Date: 2016
Source: Cancer research   76(19): 5634-5646 (Journal)
Registered Authors: Sinha, Indranil
Keywords: none
MeSH Terms:
  • Animals
  • Breast Neoplasms/drug therapy
  • Breast Neoplasms/etiology*
  • Breast Neoplasms/metabolism
  • Choline/metabolism*
  • Choline-Phosphate Cytidylyltransferase/physiology
  • Diacylglycerol Cholinephosphotransferase/physiology
  • Drug Resistance, Neoplasm
  • Estrogen Receptor alpha/physiology*
  • Female
  • Humans
  • MCF-7 Cells
  • Neoplasm Metastasis
  • Tamoxifen/therapeutic use
  • Zebrafish
PubMed: 27457520 Full text @ Cancer Res.
Estrogen receptor α (ERα) is a key regulator of breast growth and breast cancer development. Here we report how ERα impacts these processes by reprogramming metabolism in malignant breast cells. We employed an integrated approach, combining genome-wide mapping of chromatin-bound ERα with estrogen-induced transcript and metabolic profiling, to demonstrate that ERα reprograms metabolism upon estrogen stimulation, including changes in aerobic glycolysis, nucleotide and amino acid synthesis and choline (Cho) metabolism. Cho phosphotransferase CHPT1, identified as a direct ERα-regulated gene, was required for estrogen-induced effects on Cho metabolism including increased phosphatidylcholine (PtdCho) synthesis. CHPT1 silencing inhibited anchorage-independent growth and cell proliferation, also suppressing early-stage metastasis of tamoxifen (TMX)-resistant breast cancer cells in a zebrafish xenograft model. Our results showed that ERα promotes metabolic alterations in breast cancer cells mediated by its target CHPT1, which this study implicates as a candidate therapeutic target.