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Estrogen Receptor a Promotes Breast Cancer by Reprogramming Choline Metabolism
Karolinska Institute, Sweden.
Norwegian University of Science and Technology, Norway.
Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Karolinska Institute, Sweden.
Norwegian University of Science and Technology, Norway.
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2016 (English)In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 76, no 19, 5634-5646 p.Article in journal (Refereed) Published
Abstract [en]

Estrogen receptor alpha (ER alpha) is a key regulator of breast growth and breast cancer development. Here, we report how ER alpha impacts these processes by reprogramming metabolism in malignant breast cells. We employed an integrated approach, combining genome-wide mapping of chromatin-bound ER alpha with estrogeninduced transcript and metabolic profiling, to demonstrate that ER alpha reprograms metabolism upon estrogen stimulation, including changes in aerobic glycolysis, nucleotide and amino acid synthesis, and choline (Cho) metabolism. Cho phosphotransfse CHPT1, identified as a direct era-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 era promotes metabolic alterations in breast cancer cells mediated by its target CHPT1, which this study implicates as a candidate therapeutic target. (C) 2016 AACR.

Place, publisher, year, edition, pages
AMER ASSOC CANCER RESEARCH , 2016. Vol. 76, no 19, 5634-5646 p.
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Cell Biology
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URN: urn:nbn:se:liu:diva-132524DOI: 10.1158/0008-5472.CAN-15-2910ISI: 000385625500010PubMedID: 27457520OAI: oai:DiVA.org:liu-132524DiVA: diva2:1046417
Available from: 2016-11-14 Created: 2016-11-13 Last updated: 2016-11-14

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Jensen, Lasse
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Division of Cardiovascular MedicineFaculty of Medicine and Health SciencesDepartment of Clinical Pharmacology
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