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S1PR1 drives a feedforward signalling loop to regulate BATF3 and the transcriptional programme of Hodgkin lymphoma cells.

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cam.issuedOnline2017-09-07
dc.contributor.authorVrzalikova, K
dc.contributor.authorIbrahim, M
dc.contributor.authorVockerodt, M
dc.contributor.authorPerry, T
dc.contributor.authorMargielewska, S
dc.contributor.authorLupino, L
dc.contributor.authorNagy, E
dc.contributor.authorSoilleux, E
dc.contributor.authorLiebelt, D
dc.contributor.authorHollows, R
dc.contributor.authorLast, A
dc.contributor.authorReynolds, G
dc.contributor.authorAbdullah, M
dc.contributor.authorCurley, H
dc.contributor.authorCare, M
dc.contributor.authorKrappmann, D
dc.contributor.authorTooze, R
dc.contributor.authorAllegood, J
dc.contributor.authorSpiegel, S
dc.contributor.authorWei, W
dc.contributor.authorWoodman, CBJ
dc.contributor.authorMurray, PG
dc.contributor.orcidSoilleux, Elizabeth [0000-0002-4032-7249]
dc.date.accessioned2018-12-19T00:30:17Z
dc.date.available2018-12-19T00:30:17Z
dc.date.issued2018-01
dc.description.abstractThe 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.
dc.format.mediumPrint-Electronic
dc.identifier.doi10.17863/CAM.34459
dc.identifier.eissn1476-5551
dc.identifier.issn0887-6924
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/287150
dc.languageeng
dc.language.isoeng
dc.publisherSpringer Science and Business Media LLC
dc.publisher.urlhttp://dx.doi.org/10.1038/leu.2017.275
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectBasic-Leucine Zipper Transcription Factors
dc.subjectCell Line
dc.subjectCell Line, Tumor
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectHEK293 Cells
dc.subjectHodgkin Disease
dc.subjectHumans
dc.subjectPhosphatidylinositol 3-Kinases
dc.subjectReceptors, Lysosphingolipid
dc.subjectSignal Transduction
dc.subjectSphingosine-1-Phosphate Receptors
dc.subjectTranscription, Genetic
dc.subjectTumor Cells, Cultured
dc.titleS1PR1 drives a feedforward signalling loop to regulate BATF3 and the transcriptional programme of Hodgkin lymphoma cells.
dc.typeArticle
dcterms.dateAccepted2017-08-14
prism.endingPage223
prism.issueIdentifier1
prism.publicationDate2018
prism.publicationNameLeukemia
prism.startingPage214
prism.volume32
rioxxterms.licenseref.startdate2018-01
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/leu.2017.275

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