Evidence map›Paper›PMID 31142741›Full record

ArticleOncogenesis2019

RelB acts as a molecular switch driving chronic inflammation in glioblastoma multiforme.

Michael R Waters, Angela S Gupta, Karli Mockenhaupt, LaShardai N Brown, Debolina D Biswas, Tomasz Kordula

Open access · goldAbstract read
In one paragraph

Article in Oncogenesis, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 2 pooled it
3.4field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 2 syntheses or guidelines pooled it, 49 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Distinct Malignant Cell States and Myeloid Glutamate Signaling Associated with Aggressive Pancreatic Neuroendocrine Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Article
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  7. Defective Astrocyte Maturation Drives Cerebellar Neuroinflammation and Degeneration.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  8. Yin Yang 1: Function, Mechanisms, and Glia.Neurochemical research · 2025
    Review
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  10. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Michael R WatersDepartment of Biochemistry and Molecular Biology, Virginia Commonwealth, University School of Medicine and the Massey Cancer Center, Richmond, VI, 23298, USA.
Angela S GuptaDepartment of Biochemistry and Molecular Biology, Virginia Commonwealth, University School of Medicine and the Massey Cancer Center, Richmond, VI, 23298, USA.
Karli MockenhauptDepartment of Biochemistry and Molecular Biology, Virginia Commonwealth, University School of Medicine and the Massey Cancer Center, Richmond, VI, 23298, USA.
LaShardai N BrownDepartment of Biochemistry and Molecular Biology, Virginia Commonwealth, University School of Medicine and the Massey Cancer Center, Richmond, VI, 23298, USA.
Debolina D BiswasDepartment of Biochemistry and Molecular Biology, Virginia Commonwealth, University School of Medicine and the Massey Cancer Center, Richmond, VI, 23298, USA.
Tomasz KordulaDepartment of Biochemistry and Molecular Biology, Virginia Commonwealth, University School of Medicine and the Massey Cancer Center, Richmond, VI, 23298, USA. Tomasz.Kordula@vcuhealth.org.
Virginia Commonwealth University · US

Funding

Virus Vector Shared ResourceP30CA016059 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI Renato Martins · 1985 to 2026
$51.0M
Virginia Commonwealth University IRADCAK12GM093857 · NIGMS · VIRGINIA COMMONWEALTH UNIVERSITY · PI DANIEL C BULLARD, John J Ryan · 2010 to 2026
$7.0M
Ying Yang 1, a master regulator of chronic inflammation in glioblastoma multiformeR21NS102802 · NINDS · VIRGINIA COMMONWEALTH UNIVERSITY · PI KORDULA, TOMASZ K · 2018 to 2019
$427k
Cytokine-induced RelB phosphorylation in glioblastoma multiformeF30CA203447 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI GUPTA, ANGELA SATYA · 2016 to 2019
$139k
Cytokine induced RelB/p50 complexes drive mesenchymal glioma progressionF30CA200252 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI WATERS, MICHAEL · 2016 to 2019
$113k
NCI NIH HHS F30 CA200252NCI NIH HHS F30 CA203447NCI NIH HHS P30 CA016059NIGMS NIH HHS K12 GM093857NINDS NIH HHS R21 NS102802
6 · The paper itself

Abstract

Glioblastoma multiforme (GBM) is a primary brain tumor characterized by extensive necrosis and immunosuppressive inflammation. The mechanisms by which this inflammation develops and persists in GBM remain elusive. We identified two cytokines interleukin-1β (IL-1) and oncostatin M (OSM) that strongly negatively correlate with patient survival. We found that these cytokines activate RelB/p50 complexes by a canonical NF-κB pathway, which surprisingly drives expression of proinflammatory cytokines in GBM cells, but leads to their inhibition in non-transformed astrocytes. We discovered that one allele of the gene encoding deacetylase Sirtuin 1 (SIRT1), needed for repression of cytokine genes, is deleted in 80% of GBM tumors. Furthermore, RelB specifically interacts with a transcription factor Yin Yang 1 (YY1) in GBM cells and activates GBM-specific gene expression programs. As a result, GBM cells continuously secrete proinflammatory cytokines and factors attracting/activating glioma-associated microglia/macrophages and thus, promote a feedforward inflammatory loop.

Identifiers

PMID31142741
PMCPMC6541631
OpenAlexW2947006916

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.