Evidence map›Paper›PMID 28414309›Full record

ArticleOncogene2017

Tumor-derived fibulin-3 activates pro-invasive NF-κB signaling in glioblastoma cells and their microenvironment.

M S Nandhu, A Kwiatkowska, V Bhaskaran, J Hayes, B Hu, M S Viapiano

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.8field-weighted citation impact, top 16% 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

24 citing papers in PubMed, 34 citations in OpenAlex.

  1. Review
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  3. Article
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  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Molecular Mechanisms of Treatment Resistance in Glioblastoma.International journal of molecular sciences · 2020
    Review
  14. Article
  15. Review
  16. Targeting Glioblastoma Tumor Microenvironment.Advances in experimental medicine and biology · 2020
    Review
  17. Article
  18. Review
  19. Radioimmunotherapy (RIT) in Brain Tumors.Nuclear medicine and molecular imaging · 2019
    Review
  20. Article
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 4 institutions in 1 country.

M S NandhuDepartment of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
A KwiatkowskaDepartment of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
V BhaskaranDepartment of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
J HayesDepartment of Neurological Surgery, Helen Diller Family Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
B HuDepartment of Neurological Surgery, The Ohio State University, Columbus, OH, USA.
M S ViapianoDepartment of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Brigham and Women's Hospital · USHarvard University · USNeurological Surgery · USSUNY Upstate Medical University · US

Funding

Targeting the Tumor Matrix as Anti-Invasive and Sensitizing Strategy for GliomaR01CA152065 · NCI · OHIO STATE UNIVERSITY · PI VIAPIANO, MARIANO SEBASTIAN · 2010 to 2014
$1.3M
Chimeric Anti-Fibulin-3 Reagents For Targeted Therapy Of GlioblastomaR21NS091436 · NINDS · UPSTATE MEDICAL UNIVERSITY · PI VIAPIANO, MARIANO SEBASTIAN · 2015 to 2016
$852k
NCI NIH HHS R01 CA152065NINDS NIH HHS R21 NS091436
6 · The paper itself

Abstract

Molecular profiling of glioblastomas has revealed the presence of key signaling hubs that contribute to tumor progression and acquisition of resistance. One of these main signaling mechanisms is the nuclear factor-kappa B (NF-κB) pathway, which integrates multiple extracellular signals into transcriptional programs for tumor growth, invasion and maintenance of the tumor-initiating population. We show here that an extracellular protein released by glioblastoma cells, fibulin-3, drives oncogenic NF-κB in the tumor and increases NF-κB activation in peritumoral astrocytes. Fibulin-3 expression correlates with a NF-κB-regulated 'invasive signature' linked to poorer survival, being a possible tissue marker for regions of active tumor progression. Accordingly, fibulin-3 promotes glioblastoma invasion in a manner that requires NF-κB activation both in the tumor cells and their microenvironment. Mechanistically, we found that fibulin-3 activates the metalloprotease ADAM17 by competing with its endogenous inhibitor, TIMP3. This results in sustained release of soluble tumor necrosis factor alpha (TNFα) by ADAM17, which in turn activates TNF receptors and canonical NF-κB signaling. Taken together, our results underscore fibulin-3 as a novel extracellular signal with strong activating effect on NF-κB in malignant gliomas. Because fibulin-3 is produced de novo in these tumors and is absent from the normal brain, we propose that targeting the fibulin-3/NF-κB axis may provide a novel avenue to disrupt oncogenic NF-κB signaling in combination therapies for malignant brain tumors.

Indexed as

ADAM17 ProteinAnimalsBiomarkers, TumorBrain NeoplasmsCalcium-Binding ProteinsCell Line, TumorCell ProliferationDisease ProgressionGlioblastomaGliomaHumansMaleMice, NudeNeoplasm InvasivenessNF-kappa BReceptors, Tumor Necrosis FactorADAM17 ProteinBiomarkers, TumorCalcium-Binding ProteinsfibulinNF-kappa BReceptors, Tumor Necrosis FactorTumor Necrosis Factor-alpha

Identifiers

PMID28414309
PMCPMC5570669
OpenAlexW2606545932

What OpenQuestion holds

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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.