Evidence map›Paper›PMID 26500056›Full record

ArticleOncogene2016

The aryl hydrocarbon receptor links integrin signaling to the TGF-β pathway.

M Silginer, I Burghardt, D Gramatzki, L Bunse, H Leske, E J Rushing, N Hao, M Platten, M Weller, P Roth

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
3.3field-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

32 citing papers in PubMed, 59 citations in OpenAlex.

  1. Trial
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  11. The aryl hydrocarbon receptor suppresses immunity to oral squamous cell carcinoma through immune checkpoint regulation.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. The Role of Aryl Hydrocarbon Receptor (AhR) in Brain Tumors.International journal of molecular sciences · 2020
    Review
  18. Review
  19. ITGB3/CD61: a hub modulator and target in the tumor microenvironment.American journal of translational research · 2019
    Review
  20. Review
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

10 authors at 4 institutions in 3 countries.

M SilginerLaboratory of Molecular Neuro-Oncology, Department of Neurology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
I BurghardtLaboratory of Molecular Neuro-Oncology, Department of Neurology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
D GramatzkiLaboratory of Molecular Neuro-Oncology, Department of Neurology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
L BunseDepartment of Neurology, University Hospital Heidelberg, National Center for Tumor Diseases and German Cancer Consortium (DKTK) Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
H LeskeInstitute of Neuropathology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
E J RushingInstitute of Neuropathology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
N HaoSchool of Biological Sciences, University of Adelaide, Adelaide, Australia.
M PlattenDepartment of Neurology, University Hospital Heidelberg, National Center for Tumor Diseases and German Cancer Consortium (DKTK) Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
M WellerLaboratory of Molecular Neuro-Oncology, Department of Neurology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
P RothLaboratory of Molecular Neuro-Oncology, Department of Neurology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
University Hospital of Zurich · CHNational Center for Tumor Diseases · DEUniversity Hospital Heidelberg · DEUniversity of Adelaide · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Glioblastoma is the most common and aggressive form of intrinsic brain tumor. Transforming growth factor (TGF)-β represents a central mediator of the malignant phenotype of these tumors by promoting invasiveness and angiogenesis, maintaining tumor cell stemness and inducing profound immunosuppression. Integrins, which are highly expressed in glioma cells, interact with the TGF-β pathway. Furthermore, a link has been described between activity of the transcription factor aryl hydrocarbon receptor (AhR) and TGF-β expression. Here we demonstrate that integrin inhibition, using αv, β3 or β5 neutralizing antibodies, RNA interference-mediated integrin gene silencing or pharmacological inhibition by the cyclic RGD peptide EMD 121974 (cilengitide) or the non-peptidic molecule GLPG0187, inhibits AhR activity. These effects are independent of cell detachment or cell density. While AhR mRNA expression was not affected by integrin inhibition, AhR total and nuclear protein levels were reduced, suggesting that integrin inhibition-mediated regulation of AhR may occur at a post-transcriptional level. AhR-null astrocytes, AhR-null hepatocytes or glioblastoma cells with a transiently silenced AhR gene showed reduced sensitivity to integrin inhibition-mediated alterations in TGF-β signaling, indicating that AhR mediates integrin control of the TGF-β pathway. Accordingly, there was a significant correlation of αv integrin levels with nuclear AhR and pSmad2 levels as determined by immunohistochemistry in human glioblastoma in vivo. In summary, this study identifies a signaling network comprising integrins, AhR and TGF-β and validates integrin inhibition as a promising strategy not only to inhibit angiogenesis, but also to block AhR- and TGF-β-controlled features of malignancy in human glioblastoma.

Indexed as

Signal TransductionAnimalsAnimals, NewbornAntibodies, NeutralizingBrain NeoplasmsCell Line, TumorCells, CulturedGlioblastomaHepatocytesHumansImmunoblottingImmunohistochemistryIntegrinsMice, Inbred C57BLMice, KnockoutNaphthyridinesAntibodies, NeutralizingCilengitidecyclic arginine-glycine-aspartic acid peptideGLPG0187IntegrinsNaphthyridinesPeptides, CyclicReceptors, Aryl HydrocarbonSnake VenomsSulfonamidesTransforming Growth Factor beta

Identifiers

PMID26500056
OpenAlexW1870130010

What OpenQuestion holds

Textmetadata
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.