Evidence map›Paper›PMID 25890358›Full record

ArticleMolecular cancer2015

TNFα sensitizes neuroblastoma cells to FasL-, cisplatin- and etoposide-induced cell death by NF-κB-mediated expression of Fas.

Koen Mo Galenkamp, Paulina Carriba, Jorge Urresti, Laura Planells-Ferrer, Elena Coccia, Joaquín Lopez-Soriano, Bruna Barneda-Zahonero, Rana S Moubarak, Miguel F Segura, Joan X Comella

Open access · goldAbstract read
In one paragraph

Article in Molecular cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
3.1field-weighted citation impact, top 9% 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

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.

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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

10 authors at 1 institution in 1 country.

Koen Mo GalenkampCell Signaling and Apoptosis Group, Fundacio Institut de Recerca de l'Hospital Universitari de la Vall d'Hebron, Edifici Collserola, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain. koen.galenkamp@vhir.org.
Paulina CarribaCell Signaling and Apoptosis Group, Fundacio Institut de Recerca de l'Hospital Universitari de la Vall d'Hebron, Edifici Collserola, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain. paulina.carriba@gmail.com.
Jorge UrrestiCell Signaling and Apoptosis Group, Fundacio Institut de Recerca de l'Hospital Universitari de la Vall d'Hebron, Edifici Collserola, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain. jorge.urresti@vhir.org.
Laura Planells-FerrerCell Signaling and Apoptosis Group, Fundacio Institut de Recerca de l'Hospital Universitari de la Vall d'Hebron, Edifici Collserola, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain. laura.planells@vhir.org.
Elena CocciaCell Signaling and Apoptosis Group, Fundacio Institut de Recerca de l'Hospital Universitari de la Vall d'Hebron, Edifici Collserola, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain. elena.coccia@vhir.org.
Joaquín Lopez-SorianoCell Signaling and Apoptosis Group, Fundacio Institut de Recerca de l'Hospital Universitari de la Vall d'Hebron, Edifici Collserola, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain. joaquin.lopez.soriano@vhir.org.
Bruna Barneda-ZahoneroCell Signaling and Apoptosis Group, Fundacio Institut de Recerca de l'Hospital Universitari de la Vall d'Hebron, Edifici Collserola, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain. bruna.barneda@vhir.org.
Rana S MoubarakCell Signaling and Apoptosis Group, Fundacio Institut de Recerca de l'Hospital Universitari de la Vall d'Hebron, Edifici Collserola, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain. rana.moubarak@nyumc.org.
Miguel F SeguraLaboratory of Translational Research in Pediatric Cancer, Fundacio Institut de Recerca de l'Hospital Universitari de la Vall d'Hebron, Edifici Collserola, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain. miguel.segura@vhir.org.
Joan X ComellaCell Signaling and Apoptosis Group, Fundacio Institut de Recerca de l'Hospital Universitari de la Vall d'Hebron, Edifici Collserola, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain. joan.comella@vhir.org.
Vall d'Hebron Institut de Recerca · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPatients with high-risk neuroblastoma (NBL) tumors have a high mortality rate. Consequently, there is an urgent need for the development of new treatments for this condition. Targeting death receptor signaling has been proposed as an alternative to standard chemo- and radio-therapies in various tumors. In NBL, this therapeutic strategy has been largely disregarded, possibly because ~50-70% of all human NBLs are characterized by caspase-8 silencing. However, the expression of caspase-8 is detected in a significant group of NBL patients, and they could therefore benefit from treatments that induce cell death through death receptor activation. Given that cytokines, such as TNFα, are able to upregulate Fas expression, we sought to address the therapeutic relevance of co-treatment with TNFα and FasL in NBL.

methodsFor the purpose of the study we used a set of eight NBL cell lines. Here we explore the cell death induced by TNFα, FasL, cisplatin, and etoposide, or a combination thereof by Hoechst staining and calcein viability assay. Further assessment of the signaling pathways involved was performed by caspase activity assays and Western blot experiments. Characterization of Fas expression levels was achieved by qRT-PCR, cell surface biotinylation assays, and cytometry.

resultsWe have found that TNFα is able to increase FasL-induced cell death by a mechanism that involves the NF-κB-mediated induction of the Fas receptor. Moreover, TNFα sensitized NBL cells to DNA-damaging agents (i.e. cisplatin and etoposide) that induce the expression of FasL. Priming to FasL-, cisplatin-, and etoposide-induced cell death could only be achieved in NBLs that display TNFα-induced upregulation of Fas. Further analysis denotes that the high degree of heterogeneity between NBLs is also manifested in Fas expression and modulation thereof by TNFα.

conclusionsIn summary, our findings reveal that TNFα sensitizes NBL cells to FasL-induced cell death by NF-κB-mediated upregulation of Fas and unveil a new mechanism through which TNFα enhances the efficacy of currently used NBL treatments, cisplatin and etoposide.

Indexed as

Drug Resistance, NeoplasmGene Expression Regulation, NeoplasticCaspase 8Cell DeathCell Line, TumorCisplatinDeath Domain Receptor Signaling Adaptor ProteinsEnzyme ActivationEtoposideFas Ligand Proteinfas ReceptorHumansInterferon-gammaNeuroblastomaNF-kappa BTranscription, GeneticCaspase 8CisplatinDeath Domain Receptor Signaling Adaptor ProteinsEtoposideFas Ligand Proteinfas ReceptorInterferon-gammaNF-kappa BTumor Necrosis Factor-alpha

Identifiers

PMID25890358
PMCPMC4407790
OpenAlexW2159576619

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LicenceCC BY
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Registered trials

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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.