title: Estrogen Receptor α Promotes Breast Cancer by Reprogramming Choline Metabolism.
abstract: 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 synthesis. CHPT1 silencing inhibited anchorage-independent growth and cell proliferation, also suppressing early-stage metastasis of tamoxifen-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. Cancer Res; 76(19); 5634-46. ©2016 AACR.
authors.affiliation: Department of Biosciences and Nutrition, Novum, Karolinska Institutet, Huddinge, Sweden. min.jia@ki.se Karin.Dahlman-Wright@ki.se.
authors.forename: Min
authors.initials: M
authors.lastname: Jia
authors.affiliation: Department of Circulation and Medical Imaging, MR Core Facility, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Trygve
authors.initials: T
authors.lastname: Andreassen
authors.affiliation: Department of Microbiology, Tumor, and Cell Biology, Karolinska Institutet, Stockholm, Sweden. Department of Medical and Health Sciences, Unit of Cardiovascular Medicine, Linköping University, Linköping, Sweden.
authors.forename: Lasse
authors.initials: L
authors.lastname: Jensen
authors.affiliation: Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Tone Frost
authors.initials: TF
authors.lastname: Bathen
authors.affiliation: Department of Biosciences and Nutrition, Novum, Karolinska Institutet, Huddinge, Sweden.
authors.forename: Indranil
authors.initials: I
authors.lastname: Sinha
authors.affiliation: Department of Biosciences and Nutrition, Novum, Karolinska Institutet, Huddinge, Sweden.
authors.forename: Hui
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Biosciences and Nutrition, Novum, Karolinska Institutet, Huddinge, Sweden.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Biosciences and Nutrition, Novum, Karolinska Institutet, Huddinge, Sweden.
authors.forename: Lars-Arne
authors.initials: LA
authors.lastname: Haldosen
authors.affiliation: Department of Microbiology, Tumor, and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Yihai
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Oncology and Pathology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Leonard
authors.initials: L
authors.lastname: Girnita
authors.affiliation: Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Siver Andreas
authors.initials: SA
authors.lastname: Moestue
authors.affiliation: Department of Biosciences and Nutrition, Novum, Karolinska Institutet, Huddinge, Sweden. min.jia@ki.se Karin.Dahlman-Wright@ki.se.
authors.forename: Karin
authors.initials: K
authors.lastname: Dahlman-Wright
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D002794:Choline / Q000378:metabolism*; D019916:Choline-Phosphate Cytidylyltransferase / Q000502:physiology; D002798:Diacylglycerol Cholinephosphotransferase / Q000502:physiology; D019008:Drug Resistance, Neoplasm; D047628:Estrogen Receptor alpha / Q000502:physiology*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D009362:Neoplasm Metastasis; D013629:Tamoxifen / Q000627:therapeutic use; D015027:Zebrafish
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D013629:Tamoxifen; D019916:Choline-Phosphate Cytidylyltransferase; C517213:PCYT1A protein, human; D002798:Diacylglycerol Cholinephosphotransferase; D002794:Choline