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S1PR1 drives a feedforward signalling loop to regulate BATF3 and the transcriptional programme of Hodgkin lymphoma cells
K. Vrzalikova, M. Ibrahim, M. Vockerodt, T. Perry, S. Margielewska, L. Lupino, E. Nagy, E. Soilleux, D. Liebelt, R. Hollows, A. Last, G. Reynolds, M. Abdullah, H. Curley, M. Care, D. Krappmann, R. Tooze, J. Allegood, S. Spiegel, W. Wei, CBJ....
Language English Country England, Great Britain
Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
NLK
ProQuest Central
from 2000-01-01 to 1 year ago
Open Access Digital Library
from 1997-01-01
Nursing & Allied Health Database (ProQuest)
from 2000-01-01 to 1 year ago
Health & Medicine (ProQuest)
from 2000-01-01 to 1 year ago
Public Health Database (ProQuest)
from 2000-01-01 to 1 year ago
PubMed
28878352
DOI
10.1038/leu.2017.275
Knihovny.cz E-resources
- MeSH
- Cell Line MeSH
- Phosphatidylinositol 3-Kinases genetics MeSH
- Transcription, Genetic genetics MeSH
- HEK293 Cells MeSH
- Hodgkin Disease genetics MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Tumor Cells, Cultured MeSH
- Receptors, Lysosphingolipid genetics MeSH
- Gene Expression Regulation, Neoplastic genetics MeSH
- Signal Transduction genetics MeSH
- Basic-Leucine Zipper Transcription Factors genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
The Hodgkin/Reed-Sternberg cells of classical Hodgkin lymphoma (HL) are characterised by the aberrant activation of multiple signalling pathways. Here we show that a subset of HL displays altered expression of sphingosine-1-phosphate (S1P) receptors (S1PR)s. S1P activates phosphatidylinositide 3-kinase (PI3-K) in these cells that is mediated by the increased expression of S1PR1 and the decreased expression of S1PR2. We also showed that genes regulated by the PI3-K signalling pathway in HL cell lines significantly overlap with the transcriptional programme of primary HRS cells. Genes upregulated by the PI3-K pathway included the basic leucine zipper transcription factor, ATF-like 3 (BATF3), which is normally associated with the development of dendritic cells. Immunohistochemistry confirmed that BATF3 was expressed in HRS cells of most HL cases. In contrast, in normal lymphoid tissues, BATF3 expression was confined to a small fraction of CD30-positive immunoblasts. Knockdown of BATF3 in HL cell lines revealed that BATF3 contributed to the transcriptional programme of primary HRS cells, including the upregulation of S1PR1. Our data suggest that disruption of this potentially oncogenic feedforward S1P signalling loop could provide novel therapeutic opportunities for patients with HL.
Department of Cellular Pathology John Radcliffe Hospital Oxford UK
Institute of Cancer and Genomic Sciences University of Birmingham Birmingham UK
Institute of Immunology and Immunotherapy University of Birmingham Birmingham UK
Leeds Institute of Cancer and Pathology University of Leeds Leeds UK
Research Unit Cellular Signal Integration Helmholtz Zentrum München Neuherberg Germany
References provided by Crossref.org
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