Imperial College London
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DR JAMES M. FLANAGAN

Faculty of Medicine, Department of Surgery & Cancer

Reader in Epigenetics
 
 
 
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Contact

 

+44 (0)20 7594 2127j.flanagan

 
 
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Location

 

Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Lubecka:2016:carcin/bgw048,
author = {Lubecka, K and Kurzava, L and Flower, K and Buvala, H and Zhang, H and Teegarden, D and Camarillo, I and Suderman, M and Kuang, S and Andrisani, O and Flanagan, JM and Stefanska, B},
doi = {carcin/bgw048},
journal = {Carcinogenesis},
pages = {656--668},
title = {Stilbenoids remodel the DNA methylation patterns in breast cancer cells and inhibit oncogenic NOTCH signaling through epigenetic regulation of MAML2 transcriptional activity},
url = {http://dx.doi.org/10.1093/carcin/bgw048},
volume = {37},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - DNA hypomethylation was previously implicated in cancer progression and metastasis. The purpose of this study was to examine whether stilbenoids, resveratrol and pterostilbene thought to exert anticancer effects, target genes with oncogenic function for de novo methylation and silencing, leading to inactivation of related signaling pathways. Following Illumina 450K, genome-wide DNA methylation analysis reveals that stilbenoids alter DNA methylation patterns in breast cancer cells. On average, 75% of differentially methylated genes have increased methylation, and these genes are enriched for oncogenic functions, including NOTCH signaling pathway. MAML2, a coactivator of NOTCH targets, is methylated at the enhancer region and transcriptionally silenced in response to stilbenoids, possibly explaining the downregulation of NOTCH target genes. The increased DNA methylation at MAML2 enhancer coincides with increased occupancy of repressive histone marks and decrease in activating marks. This condensed chromatin structure is associated with binding of DNMT3B and decreased occupancy of OCT1 transcription factor at MAML2 enhancer, suggesting a role of DNMT3B in increasing methylation of MAML2 after stilbenoid treatment. Our results deliver a novel insight into epigenetic regulation of oncogenic signals in cancer and provide support for epigenetic-targeting strategies as an effective anticancer approach.
AU  - Lubecka,K
AU  - Kurzava,L
AU  - Flower,K
AU  - Buvala,H
AU  - Zhang,H
AU  - Teegarden,D
AU  - Camarillo,I
AU  - Suderman,M
AU  - Kuang,S
AU  - Andrisani,O
AU  - Flanagan,JM
AU  - Stefanska,B
DO  - carcin/bgw048
EP  - 668
PY  - 2016///
SN  - 1460-2180
SP  - 656
TI  - Stilbenoids remodel the DNA methylation patterns in breast cancer cells and inhibit oncogenic NOTCH signaling through epigenetic regulation of MAML2 transcriptional activity
T2  - Carcinogenesis
UR  - http://dx.doi.org/10.1093/carcin/bgw048
UR  - http://hdl.handle.net/10044/1/34646
VL  - 37
ER  -
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