S1PR1 drives a feedforward signalling loop to regulate BATF3 and the transcriptional programme of Hodgkin lymphoma cells
| العنوان: | S1PR1 drives a feedforward signalling loop to regulate BATF3 and the transcriptional programme of Hodgkin lymphoma cells |
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| المؤلفون: | Paul Murray, Lauren Lupino, Tracey Perry, Elizabeth J. Soilleux, Robert Hollows, Ciaran B J Woodman, Sandra Margielewska, Daniela Liebelt, Maha Ibrahim, Daniel Krappmann, Sarah Spiegel, Reuben Tooze, Eszter Nagy, Katerina Vrzalikova, Wenbin Wei, Martina Vockerodt, Maizaton Abdullah, Helen Curley, Mathew Care, Jeremy C. Allegood, Gary M. Reynolds |
| المساهمون: | Soilleux, Elizabeth [0000-0002-4032-7249], Apollo - University of Cambridge Repository |
| المصدر: | Leukemia Leukemia 32, 214-223 (2017) |
| بيانات النشر: | Springer Science and Business Media LLC, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Transcription, Genetic, Biology, Cell Line, Phosphatidylinositol 3-Kinases, 03 medical and health sciences, Downregulation and upregulation, Cell Line, Tumor, Tumor Cells, Cultured, Humans, Sphingosine-1-Phosphate Receptors, Transcription factor, Regulation of gene expression, Gene knockdown, HEK 293 cells, Hematology, Hodgkin Disease, Hedgehog signaling pathway, Cell biology, Gene Expression Regulation, Neoplastic, Receptors, Lysosphingolipid, Basic-Leucine Zipper Transcription Factors, HEK293 Cells, 030104 developmental biology, Oncology, Cell culture, Original Article, Signal transduction, Signal Transduction |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| تدمد: | 1476-5551 0887-6924 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6363ab5f4523a14cba9d8056db933786 https://doi.org/10.1038/leu.2017.275 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....6363ab5f4523a14cba9d8056db933786 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14765551 08876924 |
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