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A CD47-associated super-enhancer links pro-inflammatory signalling to CD47 upregulation in breast cancer

CD47 is a cell surface molecule that inhibits phagocytosis of cells that express it by binding to its receptor, SIRPα, on macrophages and other immune cells. CD47 is expressed at different levels by neoplastic and normal cells. Here, to reveal mechanisms by which different neoplastic cells generate...

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Autores principales: Betancur, Paola A., Abraham, Brian J., Yiu, Ying Y., Willingham, Stephen B., Khameneh, Farnaz, Zarnegar, Mark, Kuo, Angera H., McKenna, Kelly, Kojima, Yoko, Leeper, Nicholas J., Ho, Po, Gip, Phung, Swigut, Tomek, Sherwood, Richard I., Clarke, Michael F., Somlo, George, Young, Richard A., Weissman, Irving L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5382276/
https://www.ncbi.nlm.nih.gov/pubmed/28378740
http://dx.doi.org/10.1038/ncomms14802
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author Betancur, Paola A.
Abraham, Brian J.
Yiu, Ying Y.
Willingham, Stephen B.
Khameneh, Farnaz
Zarnegar, Mark
Kuo, Angera H.
McKenna, Kelly
Kojima, Yoko
Leeper, Nicholas J.
Ho, Po
Gip, Phung
Swigut, Tomek
Sherwood, Richard I.
Clarke, Michael F.
Somlo, George
Young, Richard A.
Weissman, Irving L.
author_facet Betancur, Paola A.
Abraham, Brian J.
Yiu, Ying Y.
Willingham, Stephen B.
Khameneh, Farnaz
Zarnegar, Mark
Kuo, Angera H.
McKenna, Kelly
Kojima, Yoko
Leeper, Nicholas J.
Ho, Po
Gip, Phung
Swigut, Tomek
Sherwood, Richard I.
Clarke, Michael F.
Somlo, George
Young, Richard A.
Weissman, Irving L.
author_sort Betancur, Paola A.
collection PubMed
description CD47 is a cell surface molecule that inhibits phagocytosis of cells that express it by binding to its receptor, SIRPα, on macrophages and other immune cells. CD47 is expressed at different levels by neoplastic and normal cells. Here, to reveal mechanisms by which different neoplastic cells generate this dominant ‘don't eat me' signal, we analyse the CD47 regulatory genomic landscape. We identify two distinct super-enhancers (SEs) associated with CD47 in certain cancer cell types. We show that a set of active constituent enhancers, located within the two CD47 SEs, regulate CD47 expression in different cancer cell types and that disruption of CD47 SEs reduces CD47 gene expression. Finally we report that the TNF-NFKB1 signalling pathway directly regulates CD47 by interacting with a constituent enhancer located within a CD47-associated SE specific to breast cancer. These results suggest that cancers can evolve SE to drive CD47 overexpression to escape immune surveillance.
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spelling pubmed-53822762017-04-21 A CD47-associated super-enhancer links pro-inflammatory signalling to CD47 upregulation in breast cancer Betancur, Paola A. Abraham, Brian J. Yiu, Ying Y. Willingham, Stephen B. Khameneh, Farnaz Zarnegar, Mark Kuo, Angera H. McKenna, Kelly Kojima, Yoko Leeper, Nicholas J. Ho, Po Gip, Phung Swigut, Tomek Sherwood, Richard I. Clarke, Michael F. Somlo, George Young, Richard A. Weissman, Irving L. Nat Commun Article CD47 is a cell surface molecule that inhibits phagocytosis of cells that express it by binding to its receptor, SIRPα, on macrophages and other immune cells. CD47 is expressed at different levels by neoplastic and normal cells. Here, to reveal mechanisms by which different neoplastic cells generate this dominant ‘don't eat me' signal, we analyse the CD47 regulatory genomic landscape. We identify two distinct super-enhancers (SEs) associated with CD47 in certain cancer cell types. We show that a set of active constituent enhancers, located within the two CD47 SEs, regulate CD47 expression in different cancer cell types and that disruption of CD47 SEs reduces CD47 gene expression. Finally we report that the TNF-NFKB1 signalling pathway directly regulates CD47 by interacting with a constituent enhancer located within a CD47-associated SE specific to breast cancer. These results suggest that cancers can evolve SE to drive CD47 overexpression to escape immune surveillance. Nature Publishing Group 2017-04-05 /pmc/articles/PMC5382276/ /pubmed/28378740 http://dx.doi.org/10.1038/ncomms14802 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Betancur, Paola A.
Abraham, Brian J.
Yiu, Ying Y.
Willingham, Stephen B.
Khameneh, Farnaz
Zarnegar, Mark
Kuo, Angera H.
McKenna, Kelly
Kojima, Yoko
Leeper, Nicholas J.
Ho, Po
Gip, Phung
Swigut, Tomek
Sherwood, Richard I.
Clarke, Michael F.
Somlo, George
Young, Richard A.
Weissman, Irving L.
A CD47-associated super-enhancer links pro-inflammatory signalling to CD47 upregulation in breast cancer
title A CD47-associated super-enhancer links pro-inflammatory signalling to CD47 upregulation in breast cancer
title_full A CD47-associated super-enhancer links pro-inflammatory signalling to CD47 upregulation in breast cancer
title_fullStr A CD47-associated super-enhancer links pro-inflammatory signalling to CD47 upregulation in breast cancer
title_full_unstemmed A CD47-associated super-enhancer links pro-inflammatory signalling to CD47 upregulation in breast cancer
title_short A CD47-associated super-enhancer links pro-inflammatory signalling to CD47 upregulation in breast cancer
title_sort cd47-associated super-enhancer links pro-inflammatory signalling to cd47 upregulation in breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5382276/
https://www.ncbi.nlm.nih.gov/pubmed/28378740
http://dx.doi.org/10.1038/ncomms14802
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