Evidence map›Paper›PMID 38806726›Full record

ArticleBritish journal of cancer2024

Nuclear factor-κB activation by transforming growth factor-β1 drives tumour microenvironment-mediated drug resistance in neuroblastoma.

Kévin Louault, Laurence Blavier, Men-Hua Lee, Rebekah J Kennedy, G Esteban Fernandez, Bruce R Pawel, Shahab Asgharzadeh, Yves A DeClerck

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
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

10 citing papers in PubMed.

  1. Article
  2. lncRNACancers · 2026
    Article
  3. Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. 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

8 authors.

Kévin LouaultCancer and Blood Diseases Institute, Department of Pediatrics, Children's Hospital Los Angeles and the University of Southern California, Los Angeles, CA, 90027, USA.
Laurence BlavierCancer and Blood Diseases Institute, Department of Pediatrics, Children's Hospital Los Angeles and the University of Southern California, Los Angeles, CA, 90027, USA.
Men-Hua LeeCancer and Blood Diseases Institute, Department of Pediatrics, Children's Hospital Los Angeles and the University of Southern California, Los Angeles, CA, 90027, USA.
Rebekah J KennedyCancer and Blood Diseases Institute, Department of Pediatrics, Children's Hospital Los Angeles and the University of Southern California, Los Angeles, CA, 90027, USA.
G Esteban FernandezThe Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, 90027, USA.
Bruce R PawelDepartment of Pathology, and Laboratory Medicine, Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
Shahab AsgharzadehCancer and Blood Diseases Institute, Department of Pediatrics, Children's Hospital Los Angeles and the University of Southern California, Los Angeles, CA, 90027, USA.
Yves A DeClerckCancer and Blood Diseases Institute, Department of Pediatrics, Children's Hospital Los Angeles and the University of Southern California, Los Angeles, CA, 90027, USA. ydeclerck@chla.usc.edu.ORCID 0000-0002-3688-0113

Funding

Tumor microenvironment-dependent therapy resistanceP01CA217959 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI JOHN M MARIS · 2017 to 2026
$20.7M
Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) CA217959-06NCI NIH HHS P01 CA217959
6 · The paper itself

Abstract

backgroundIntrinsic and extrinsic factors in the tumour microenvironment (TME) contribute to therapeutic resistance. Here we demonstrate that transforming growth factor (TGF)-β1 produced in the TME increased drug resistance of neuroblastoma (NB) cells.

methodsHuman NB cell lines were tested in vitro for their sensitivity to Doxorubicin (DOX) and Etoposide (ETOP) in the presence of tumour-associated macrophages (TAM) and mesenchymal stromal cells/cancer-associated fibroblasts (MSC/CAF). These experiments were validated in xenotransplanted and primary tumour samples.

resultsDrug resistance was associated with an increased expression of efflux transporter and anti-apoptotic proteins. Upregulation was dependent on activation of nuclear factor (NF)-κB by TGF-β-activated kinase (TAK1) and SMAD2. Resistance was reversed upon pharmacologic and genetic inhibitions of NF-κB, and TAK1/SMAD2. Interleukin-6, leukaemia inhibitory factor and oncostatin M were upregulated by this TGF-β/TAK1/NF-κB/SMAD2 signalling pathway contributing to drug resistance via an autocrine loop activating STAT3. An analysis of xenotransplanted NB tumours revealed an increased presence of phospho (p)-NF-κB in tumours co-injected with MSC/CAF and TAM, and these tumours failed to respond to Etoposide but responded if treated with a TGF-βR1/ALK5 inhibitor. Nuclear p-NF-κB was increased in patient-derived tumours rich in TME cells.

conclusionsThe data provides a novel insight into a targetable mechanism of environment-mediated drug resistance.

Indexed as

DoxorubicinDrug Resistance, NeoplasmNeuroblastomaNF-kappa BTransforming Growth Factor beta1Tumor MicroenvironmentAnimalsCancer-Associated FibroblastsCell Line, TumorEtoposideHumansMAP Kinase Kinase Kinase 7MAP Kinase Kinase KinasesMiceSignal TransductionSmad2 ProteinDoxorubicinEtoposideMAP Kinase Kinase Kinase 7MAP Kinase Kinase KinasesNF-kappa BSmad2 ProteinSMAD2 protein, humanTGFB1 protein, humanTransforming Growth Factor beta1

Identifiers

PMID38806726
PMCPMC11231159

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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.