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Single-Cell Transcriptome Analysis Reveals Estrogen Signaling Coordinately Augments One-Carbon, Polyamine, and Purine Synthesis in Breast Cancer
Zhu D.1; Zhao Z.1; Cui G.1; Chang S.1; Hu L.1; See Y.X.1; Lim M.G.L.3; Guo D.1; Chen X.1; Robson P.3; Luo Y.2; Cheung E.1
2018-11-20
Source PublicationCell Reports
ISSN22111247
Volume25Issue:8Pages:2285-2298.e4
Abstract

Estrogen drives breast cancer (BCa) progression by directly activating estrogen receptor α (ERα). However, because of the stochastic nature of gene transcription, it is important to study the estrogen signaling pathway at the single-cell level to fully understand how ERα regulates transcription. Here, we performed single-cell transcriptome analysis on ERα-positive BCa cells following 17β-estradiol stimulation and reconstructed the dynamic estrogen-responsive transcriptional network from discrete time points into a pseudotemporal continuum. Notably, differentially expressed genes show an estrogen-stimulated metabolic switch that favors biosynthesis but reduces estrogen degradation. Moreover, folate-mediated one-carbon metabolism is reprogrammed through the mitochondrial folate pathway and polyamine and purine synthesis are upregulated coordinately. Finally, we show AZIN1 and PPAT are direct ERα targets that are essential for BCa cell survival and growth. In summary, our study highlights the dynamic transcriptional heterogeneity in ERα-positive BCa cells upon estrogen stimulation and uncovers a mechanism of estrogen-mediated metabolic switch. Zhu et al. perform single-cell RNA-seq to reveal a dynamic transcriptional network in ERα+ breast cancer cells following estrogen stimulation and show that estrogen signaling promotes breast cancer cell survival and growth by mediating a metabolic switch in which folate-mediated one-carbon metabolism is reprogrammed via the mitochondrial folate pathway.

KeywordBreast Cancer Estrogen Receptor α Metabolic Switch Single-cell Rna Sequencing
DOI10.1016/j.celrep.2018.10.093
URLView the original
Indexed BySCI
Language英语
WOS Research AreaCell Biology
WOS SubjectCell Biology
WOS IDWOS:000450794200025
PublisherCELL PRESS
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Cited Times [WOS]:4   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.Universidade de Macau
2.Guangzhou Medical University
3.A-Star, Genome Institute of Singapore
Recommended Citation
GB/T 7714
Zhu D.,Zhao Z.,Cui G.,et al. Single-Cell Transcriptome Analysis Reveals Estrogen Signaling Coordinately Augments One-Carbon, Polyamine, and Purine Synthesis in Breast Cancer[J]. Cell Reports,2018,25(8):2285-2298.e4.
APA Zhu D..,Zhao Z..,Cui G..,Chang S..,Hu L..,...&Cheung E..(2018).Single-Cell Transcriptome Analysis Reveals Estrogen Signaling Coordinately Augments One-Carbon, Polyamine, and Purine Synthesis in Breast Cancer.Cell Reports,25(8),2285-2298.e4.
MLA Zhu D.,et al."Single-Cell Transcriptome Analysis Reveals Estrogen Signaling Coordinately Augments One-Carbon, Polyamine, and Purine Synthesis in Breast Cancer".Cell Reports 25.8(2018):2285-2298.e4.
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