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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....
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem
NLK
ProQuest Central
od 2000-01-01 do Před 1 rokem
Open Access Digital Library
od 1997-01-01
Nursing & Allied Health Database (ProQuest)
od 2000-01-01 do Před 1 rokem
Health & Medicine (ProQuest)
od 2000-01-01 do Před 1 rokem
Public Health Database (ProQuest)
od 2000-01-01 do Před 1 rokem
PubMed
28878352
DOI
10.1038/leu.2017.275
Knihovny.cz E-zdroje
- MeSH
- buněčné linie MeSH
- fosfatidylinositol-3-kinasy genetika MeSH
- genetická transkripce genetika MeSH
- HEK293 buňky MeSH
- Hodgkinova nemoc genetika MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádorové buňky kultivované MeSH
- receptory lysosfingolipidů genetika MeSH
- regulace genové exprese u nádorů genetika MeSH
- signální transdukce genetika MeSH
- transkripční faktory bZIP genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem 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
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