PUBLICATION
Estrogen receptor ? promotes breast cancer by reprogramming choline metabolism
- Authors
- 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.
- ID
- ZDB-PUB-160728-16
- Date
- 2016
- Source
- Cancer research 76(19): 5634-5646 (Journal)
- Registered Authors
- Sinha, Indranil
- Keywords
- none
- MeSH Terms
-
- Breast Neoplasms/drug therapy
- Breast Neoplasms/etiology*
- Breast Neoplasms/metabolism
- Humans
- Drug Resistance, Neoplasm
- Choline-Phosphate Cytidylyltransferase/physiology
- Zebrafish
- Diacylglycerol Cholinephosphotransferase/physiology
- Tamoxifen/therapeutic use
- Animals
- Female
- Estrogen Receptor alpha/physiology*
- Choline/metabolism*
- Neoplasm Metastasis
- MCF-7 Cells
- PubMed
- 27457520 Full text @ Cancer Res.
Citation
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. (2016) Estrogen receptor ? promotes breast cancer by reprogramming choline metabolism. Cancer research. 76(19):5634-5646.
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 (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.
Errata / Notes
This article is corrected by ZDB-PUB-220906-175 .
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping