The NF-κB RelB Protein Is an Oncogenic Driver of Mesenchymal Glioma
Publication Date
February 25, 2013
Journal
PLOS ONE
Authors
Dong Whan Lee, Dhivya Ramakrishnan, John Valenta, Ian F. Parney, et al
Volume
8
Issue
2
Pages
e57489
DOI
https://dx.plos.org/10.1371/journal.pone.0057489
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0057489
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/23451236
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581451
Europe PMC
http://europepmc.org/abstract/MED/23451236
Web of Science
000316849500109
Scopus
84874362151
Mendeley
http://www.mendeley.com/research/nf%CE%BAb-relb-protein-oncogenic-driver-mesenchymal-glioma
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Mendeley | Further Information

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Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/970463"], "description"=>"<p><i>(A)</i> Quantitative real-time PCR (qRT-PCR) was performed to analyze expression of the indicated mesenchymal and epithelial genes. <i>(B)</i> Western blot analysis with the indicated antibodies was performed on U87 cells expressing control or two independent RelB shRNAs (shRelB-1 and shRelB-3). The accompanying graph shows quantified protein levels in control (shCon) and RelB knockdown cells. <i>(C)</i> qRT-PCR analysis of <i>OLIG2</i> mRNA levels in shControl and shRelB cells, <i>(D)</i> qRT-PCR analysis of <i>OLIG2</i> mRNA levels in RelB knockdown cells that contain vector control or rescued mRelB expression. <i>(E)</i> qRT-PCR analysis of <i>OLIG2</i> and YKL-40 expression in wild type U87 glioma cells that overexpress mRelB.</p>", "links"=>[], "tags"=>["controls", "genes"], "article_id"=>639717, "categories"=>["Cancer", "Genetics"], "users"=>["Dong Whan Lee", "Dhivya Ramakrishnan", "John Valenta", "Ian F. Parney", "Kayla J. Bayless", "Raquel Sitcheran"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0057489.g003", "stats"=>{"downloads"=>1, "page_views"=>49, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_RelB_controls_the_expression_of_genes_associated_with_EMT_/639717", "title"=>"RelB controls the expression of genes associated with EMT.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-26 11:05:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/970481", "https://ndownloader.figshare.com/files/970483", "https://ndownloader.figshare.com/files/970485"], "description"=>"<div><p>High-grade gliomas, such as glioblastomas (GBMs), are very aggressive, invasive brain tumors with low patient survival rates. The recent identification of distinct glioma tumor subtypes offers the potential for understanding disease pathogenesis, responses to treatment and identification of molecular targets for personalized cancer therapies. However, the key alterations that drive tumorigenesis within each subtype are still poorly understood. Although aberrant NF-κB activity has been implicated in glioma, the roles of specific members of this protein family in tumorigenesis and pathogenesis have not been elucidated. In this study, we show that the NF-κB protein RelB is expressed in a particularly aggressive mesenchymal subtype of glioma, and loss of RelB significantly attenuated glioma cell survival, motility and invasion. We find that RelB promotes the expression of mesenchymal genes including YKL-40, a marker of the MES glioma subtype. Additionally, RelB regulates expression of Olig2, a regulator of cancer stem cell proliferation and a candidate marker for the cell of origin in glioma. Furthermore, loss of RelB in glioma cells significantly diminished tumor growth in orthotopic mouse xenografts. The relevance of our studies for human disease was confirmed by analysis of a human GBM genome database, which revealed that high RelB expression strongly correlates with rapid tumor progression and poor patient survival rates. Thus, our findings demonstrate that RelB is an oncogenic driver of mesenchymal glioma tumor growth and invasion, highlighting the therapeutic potential of inhibiting the noncanonical NF-κB (RelB-mediated) pathway to treat these deadly tumors.</p> </div>", "links"=>[], "tags"=>["relb", "oncogenic", "mesenchymal", "glioma"], "article_id"=>639735, "categories"=>["Cancer", "Genetics"], "users"=>["Dong Whan Lee", "Dhivya Ramakrishnan", "John Valenta", "Ian F. Parney", "Kayla J. Bayless", "Raquel Sitcheran"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0057489.s001", "https://dx.doi.org/10.1371/journal.pone.0057489.s002", "https://dx.doi.org/10.1371/journal.pone.0057489.s003"], "stats"=>{"downloads"=>7, "page_views"=>45, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/The_NF_B_RelB_Protein_Is_an_Oncogenic_Driver_of_Mesenchymal_Glioma__/639735", "title"=>"The NF-κB RelB Protein Is an Oncogenic Driver of Mesenchymal Glioma", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-02-26 11:08:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/970468"], "description"=>"<p><i>(A)</i> Subcutaneous xenografts of DiD-labeled U87 shControl and shRelB-1 cells were allowed to grow for 4 weeks (n = 4). Average volume of tumors was determined based on caliper measurement of tumor diameter. Inset shows representative <i>in vivo</i> tumor images taken with an <i>In Vivo</i> Kodak FX Imager. <i>(B)</i> Orthotopic intracranial injection of DiD-labeled U87 shControl, shRelB-1 and shRelB-3 cells were allowed to grow for 4 weeks. Representative <i>in vivo</i> tumor images from one experiment are shown (n = 3). <i>(C)</i> Western blot analysis was performed on patient-derived glioma cells. <i>(D)</i> Comparison of RelB protein and mRNA levels among the indicated cells. To compare RelB protein expression in U87 and BT cells, western blot data from <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057489#pone-0057489-g001\" target=\"_blank\">Figs. 1A</a> and <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057489#pone-0057489-g005\" target=\"_blank\">5B</a> were quantified and normalized to Actin. RelB mRNA levels were quantified by real-time PCR. <i>(E)</i> Intracranial tumor growth of DiD-labeled BT25 glioma cells expressing shRNA control or shRNA-RelB-3 was evaluated by <i>in vivo</i> fluorescence imaging 4 weeks after intracranial innoculation. Representative tumor images from one experiment are shown (n = 3). Similar results were seen with shRelB-1 cells (data not shown). (F) H&E and KI67 staining of frozen brain sections after 4 weeks of tumor growth. Yellow arrows indicate tumor borders. <i>(G)</i> Western blot analysis of RelB levels in BT25 shControl and shRelB-3 cells.</p>", "links"=>[], "tags"=>["controls", "tumorigenesis", "glioma", "prognostic"], "article_id"=>639722, "categories"=>["Cancer", "Genetics"], "users"=>["Dong Whan Lee", "Dhivya Ramakrishnan", "John Valenta", "Ian F. Parney", "Kayla J. Bayless", "Raquel Sitcheran"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0057489.g004", "stats"=>{"downloads"=>1, "page_views"=>52, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_RelB_controls_tumorigenesis_glioma_tumorigenesis_in_vivo_and_is_a_prognostic_indicator_of_glioma_patient_survival_/639722", "title"=>"RelB controls tumorigenesis glioma tumorigenesis <i>in vivo</i> and is a prognostic indicator of glioma patient survival.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-26 11:05:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/970457"], "description"=>"<p><i>In vitro</i> scratch assays were performed to compare the motility of <i>(A)</i> U87 cells expressing shRNA control, shRelB-1 cells, shRelB-1+vector and shRelB+mRelB; <i>(B)</i> U87 cells expressing pLenti6 vector, pLenti6-mRelB, or pLenti6-hRelB. Photographs were taken of cells pre-scratch, 0 hours and 20–24 hours post-scratch. <i>(C)</i> Western blot was performed on U87 wild type or shRelB-3 cells using antibodies to RelB and actin. (D<i>)</i> Representative photographs of a side view of U87 cells invading three-dimensional collagen matrices. Arrow indicates the surface of the collagen matrix. <i>(E)</i> Average numbers of invading cells per field from 3 independent fields (+/− SD). <i>(F)</i> Average invasion distances (n = 100 cells) +/− SEM. <i>(G)</i> Representative photographs of a side view of U87-shRelB cell invasion +/− rescue with mRelB. <i>(H)</i> Quantification of number of invading cells from <i>G</i>. <i>(I)</i> invasion distance from G. Data shown are average numbers of invading cells per field from 3 independent fields (+/− SD). <i>(J)</i> Representative photographs of a side view of U87 cells overexpressing hRelB invading collagen matrices. <i>(K)</i> Quantification of invasion from J. Data shown are average numbers of invading cells per field from 3 independent fields (+/− SD). <i>(L)</i> Invasion distance from panel J.</p>", "links"=>[], "tags"=>["controls", "glioma", "motility"], "article_id"=>639711, "categories"=>["Cancer", "Genetics"], "users"=>["Dong Whan Lee", "Dhivya Ramakrishnan", "John Valenta", "Ian F. Parney", "Kayla J. Bayless", "Raquel Sitcheran"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0057489.g002", "stats"=>{"downloads"=>2, "page_views"=>44, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_RelB_controls_glioma_cell_motility_and_invasion_/639711", "title"=>"RelB controls glioma cell motility and invasion.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-26 11:04:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/970452"], "description"=>"<p><i>(A)</i> Western blot analysis of glioma cells using indicated antibodies. <i>(B)</i> Western blot analysis was used to assess RelB expression in U87 cells stably expressing a scrambled shRNA control or RelB targeting shRNAs. <i>(C)</i> MTS assays performed on U87 shRNA control, shRelB-1 and shRelB-3 cell lines. Error bars indicate standard deviation (SD), n = 4. <i>(D)</i> A Bioluminescent assay to measure Caspase 3/7 activity was performed on U87 cells expressing the indicated shRNA constructs. Error bars indicate SD. <i>(E)</i> Quantitative real-time PCR examining levelsof Bcl-2 and c-FLIP mRNA in RelB knockdown cells. Error bars indicate standard error (n = 3).</p>", "links"=>[], "tags"=>["glioma", "proliferation"], "article_id"=>639706, "categories"=>["Cancer", "Genetics"], "users"=>["Dong Whan Lee", "Dhivya Ramakrishnan", "John Valenta", "Ian F. Parney", "Kayla J. Bayless", "Raquel Sitcheran"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0057489.g001", "stats"=>{"downloads"=>2, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_RelB_promotes_glioma_cell_proliferation_and_survival_/639706", "title"=>"RelB promotes glioma cell proliferation and survival.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-26 11:03:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/970473"], "description"=>"<p>Kaplan-Meier curves from TCGA (The Cancer Genome Atlas) data analysis show the effect of RelB overexpression on time for tumor progression <i>(A)</i> and patient survival <i>(B)</i>.</p>", "links"=>[], "tags"=>["curves", "TCGA", "cancer", "genome", "relb", "overexpression", "progression"], "article_id"=>639727, "categories"=>["Cancer", "Genetics"], "users"=>["Dong Whan Lee", "Dhivya Ramakrishnan", "John Valenta", "Ian F. Parney", "Kayla J. Bayless", "Raquel Sitcheran"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0057489.g005", "stats"=>{"downloads"=>6, "page_views"=>633, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Kaplan_Meier_curves_from_TCGA_The_Cancer_Genome_Atlas_data_analysis_show_the_effect_of_RelB_overexpression_on_time_for_tumor_progression_A_and_patient_survival_B_/639727", "title"=>"Kaplan-Meier curves from TCGA (The Cancer Genome Atlas) data analysis show the effect of RelB overexpression on time for tumor progression <i>(A)</i> and patient survival <i>(B)</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-26 11:06:37"}

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Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Developmental biology", "average_usage"=>[275, 472, 605, 720, 822, 921, 1013, 1106, 1200, 1289, 1378, 1459, 1531]}, {"subject_area"=>"/Medicine and health sciences/Oncology", "average_usage"=>[249, 468, 599, 718, 820, 920, 1008, 1093, 1181, 1281, 1357, 1444, 1517]}]}
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