BCL11B is up-regulated by EWS/FLI and contributes to the transformed phenotype in Ewing sarcoma.

The EWS/FLI translocation product is the causative oncogene in Ewing sarcoma and acts as an aberrant transcription factor. EWS/FLI dysregulates gene expression during tumorigenesis by abnormally activating or repressing genes. The expression levels of thousands of genes are affected in Ewing sarcoma...

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Autores principales:	Elizabeth T Wiles, Bianca Lui-Sargent, Russell Bell, Stephen L Lessnick
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6116bd5bc3a94646a34c47a8b40bb2a9
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spelling	oai:doaj.org-article:6116bd5bc3a94646a34c47a8b40bb2a92021-11-18T07:52:51ZBCL11B is up-regulated by EWS/FLI and contributes to the transformed phenotype in Ewing sarcoma.1932-620310.1371/journal.pone.0059369https://doaj.org/article/6116bd5bc3a94646a34c47a8b40bb2a92013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23527175/?tool=EBIhttps://doaj.org/toc/1932-6203The EWS/FLI translocation product is the causative oncogene in Ewing sarcoma and acts as an aberrant transcription factor. EWS/FLI dysregulates gene expression during tumorigenesis by abnormally activating or repressing genes. The expression levels of thousands of genes are affected in Ewing sarcoma, however, it is unknown which of these genes contribute to the transformed phenotype. Here we characterize BCL11B as an up-regulated EWS/FLI target that is necessary for the maintenance of transformation in patient derived Ewing sarcoma cells lines. BCL11B, a zinc finger transcription factor, acts as a transcriptional repressor in Ewing's sarcoma and contributes to the EWS/FLI repressed gene signature. BCL11B repressive activity is mediated by the NuRD co-repressor complex. We further demonstrate that re-expression of SPRY1, a repressed target of BCL11B, limits the transformation capacity of Ewing sarcoma cells. These data define a new pathway downstream of EWS/FLI required for oncogenic maintenance in Ewing sarcoma.Elizabeth T WilesBianca Lui-SargentRussell BellStephen L LessnickPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e59369 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elizabeth T Wiles Bianca Lui-Sargent Russell Bell Stephen L Lessnick BCL11B is up-regulated by EWS/FLI and contributes to the transformed phenotype in Ewing sarcoma.
description	The EWS/FLI translocation product is the causative oncogene in Ewing sarcoma and acts as an aberrant transcription factor. EWS/FLI dysregulates gene expression during tumorigenesis by abnormally activating or repressing genes. The expression levels of thousands of genes are affected in Ewing sarcoma, however, it is unknown which of these genes contribute to the transformed phenotype. Here we characterize BCL11B as an up-regulated EWS/FLI target that is necessary for the maintenance of transformation in patient derived Ewing sarcoma cells lines. BCL11B, a zinc finger transcription factor, acts as a transcriptional repressor in Ewing's sarcoma and contributes to the EWS/FLI repressed gene signature. BCL11B repressive activity is mediated by the NuRD co-repressor complex. We further demonstrate that re-expression of SPRY1, a repressed target of BCL11B, limits the transformation capacity of Ewing sarcoma cells. These data define a new pathway downstream of EWS/FLI required for oncogenic maintenance in Ewing sarcoma.
format	article
author	Elizabeth T Wiles Bianca Lui-Sargent Russell Bell Stephen L Lessnick
author_facet	Elizabeth T Wiles Bianca Lui-Sargent Russell Bell Stephen L Lessnick
author_sort	Elizabeth T Wiles
title	BCL11B is up-regulated by EWS/FLI and contributes to the transformed phenotype in Ewing sarcoma.
title_short	BCL11B is up-regulated by EWS/FLI and contributes to the transformed phenotype in Ewing sarcoma.
title_full	BCL11B is up-regulated by EWS/FLI and contributes to the transformed phenotype in Ewing sarcoma.
title_fullStr	BCL11B is up-regulated by EWS/FLI and contributes to the transformed phenotype in Ewing sarcoma.
title_full_unstemmed	BCL11B is up-regulated by EWS/FLI and contributes to the transformed phenotype in Ewing sarcoma.
title_sort	bcl11b is up-regulated by ews/fli and contributes to the transformed phenotype in ewing sarcoma.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/6116bd5bc3a94646a34c47a8b40bb2a9
work_keys_str_mv	AT elizabethtwiles bcl11bisupregulatedbyewsfliandcontributestothetransformedphenotypeinewingsarcoma AT biancaluisargent bcl11bisupregulatedbyewsfliandcontributestothetransformedphenotypeinewingsarcoma AT russellbell bcl11bisupregulatedbyewsfliandcontributestothetransformedphenotypeinewingsarcoma AT stephenllessnick bcl11bisupregulatedbyewsfliandcontributestothetransformedphenotypeinewingsarcoma
_version_	1718422814766137344

BCL11B is up-regulated by EWS/FLI and contributes to the transformed phenotype in Ewing sarcoma.

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