Evidence map›Paper›PMID 25088200›Full record

ArticleOncogene2015

The p38-MK2-HuR pathway potentiates EGFRvIII-IL-1β-driven IL-6 secretion in glioblastoma cells.

F M S Gurgis, Y T Yeung, M X M Tang, B Heng, M Buckland, A J Ammit, J Haapasalo, H Haapasalo, G J Guillemin, T Grewal and 1 more

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 1 pooled it
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

46 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.

  1. Pooled it
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  10. [Coactivator p300-induced H3K27 acetylation mediates lipopolysaccharide-induced inflammatory mediator synthesis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022
    Article
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  14. Adipocyte-specific deletion of HuR induces spontaneous cardiac hypertrophy and fibrosis.American journal of physiology. Heart and circulatory physiology · 2021
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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

11 authors at 3 institutions in 2 countries.

F M S GurgisSchool of Medical Sciences/Pharmacology, University of Sydney, New South Wales, Australia.
Y T Yeung1] School of Medical Sciences/Pharmacology, University of Sydney, New South Wales, Australia [2] Faculty of Pharmacy, University of Sydney, New South Wales, Australia.
M X M TangSchool of Medical Sciences/Pharmacology, University of Sydney, New South Wales, Australia.
B HengAustralian School of Advanced Medicine, Macquarie University, New South Wales, Australia.
M BucklandSchool of Medical Sciences/Pathology, University of Sydney, New South Wales, Australia.
A J AmmitFaculty of Pharmacy, University of Sydney, New South Wales, Australia.
J Haapasalo1] Tampere University Hospital, Department of Pathology and Fimlab laboratories, Tampere, Finland [2] Tampere University Hospital, Unit of Neurosurgery, Tampere, Finland.
H HaapasaloTampere University Hospital, Department of Pathology and Fimlab laboratories, Tampere, Finland.
G J GuilleminAustralian School of Advanced Medicine, Macquarie University, New South Wales, Australia.ORCID 0000000181054470
T GrewalFaculty of Pharmacy, University of Sydney, New South Wales, Australia.
L MunozSchool of Medical Sciences/Pharmacology, University of Sydney, New South Wales, Australia.
The University of Sydney · AUMacquarie University · AUTampere University Hospital · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The microenvironment of glioblastoma (GBM) contains high levels of inflammatory cytokine interleukin 6 (IL-6), which contributes to promote tumour progression and invasion. The common epidermal growth factor receptor variant III (EGFRvIII) mutation in GBM is associated with significantly higher levels of IL-6. Furthermore, elevated IL-1β levels in GBM tumours are also believed to activate GBM cells and enhance IL-6 production. However, the crosstalk between these intrinsic and extrinsic factors within the oncogene-microenvironment of GBM causing overproduction of IL-6 is poorly understood. Here, we show that EGFRvIII potentiates IL-1β-induced IL-6 secretion from GBM cells. Importantly, exacerbation of IL-6 production is most effectively attenuated in EGFRvIII-expressing GBM cells with inhibitors of p38 mitogen-activated protein kinase (p38 MAPK) and MAPK-activated protein kinase 2 (MK2). Enhanced IL-6 production and increased sensitivity toward pharmacological p38 MAPK and MK2 inhibitors in EGFRvIII-expressing GBM cells is associated with increased MK2-dependent nuclear-cytoplasmic shuttling and accumulation of human antigen R (HuR), an IL-6 mRNA-stabilising protein, in the cytosol. IL-1β-stimulated activation of the p38 MAPK-MK2-HuR pathway significantly enhances IL-6 mRNA stability in GBM cells carrying EGFRvIII. Further supporting a role for the p38 MAPK-MK2-HuR pathway in the development of inflammatory environment in GBM, activated MK2 is found in more than 50% of investigated GBM tissues and correlates with lower grade and secondary GBMs. Taken together, p38 MAPK-MK2-HuR signalling may enhance the potential of intrinsic (EGFRvIII) and extrinsic (IL-1β) factors to develop an inflammatory GBM environment. Hence, further improvement of brain-permeable and anti-inflammatory inhibitors targeting p38 MAPK, MK2 and HuR may combat progression of lower grade gliomas into aggressive GBMs.

Indexed as

Brain NeoplasmsGlioblastomaELAV-Like Protein 1ELAV ProteinsErbB ReceptorsHumansInflammationInterleukin-1betaInterleukin-6Intracellular Signaling Peptides and ProteinsMAP-Kinase-Activated Kinase 2MAP Kinase Signaling Systemp38 Mitogen-Activated Protein KinasesProtein Serine-Threonine KinasesTumor Cells, CulturedTumor MicroenvironmentELAVL1 protein, humanELAV-Like Protein 1ELAV Proteinsepidermal growth factor receptor VIIIErbB ReceptorsIL6 protein, humanInterleukin-1betaInterleukin-6Intracellular Signaling Peptides and ProteinsMAP-Kinase-Activated Kinase 2p38 Mitogen-Activated Protein KinasesProtein Serine-Threonine Kinases

Identifiers

PMID25088200
OpenAlexW2331032789

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.