Evidence map›Paper›PMID 29470550›Full record

ArticlePloS one2018

The pregnane X receptor (PXR) and the nuclear receptor corepressor 2 (NCoR2) modulate cell growth in head and neck squamous cell carcinoma.

Juan Pablo Rigalli, Matthias Reichel, Tasmin Reuter, Guillermo Nicolás Tocchetti, Gerhard Dyckhoff, Christel Herold-Mende, Dirk Theile, Johanna Weiss

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

Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.3field-weighted citation impact, top 19% 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

4 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
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  3. Review
  4. 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

8 authors at 2 institutions in 2 countries.

Juan Pablo RigalliDepartment of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Heidelberg, Germany.
Matthias ReichelDepartment of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Heidelberg, Germany.
Tasmin ReuterDepartment of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Heidelberg, Germany.
Guillermo Nicolás TocchettiDepartment of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Heidelberg, Germany.
Gerhard DyckhoffMolecular Cell Biology Group, Department of Otorhinolaryngology, Head and Neck Surgery, University of Heidelberg, Heidelberg, Germany.
Christel Herold-MendeMolecular Cell Biology Group, Department of Otorhinolaryngology, Head and Neck Surgery, University of Heidelberg, Heidelberg, Germany.
Dirk TheileDepartment of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Heidelberg, Germany.
Johanna WeissDepartment of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Heidelberg, Germany.ORCID 0000-0002-2034-923X
Heidelberg University · DEConsejo Nacional de Investigaciones Científicas y Técnicas · AR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth most frequent cancer worldwide. The pregnane X receptor (PXR) is a nuclear receptor regulating several target genes associated with cancer malignancy. We here demonstrated a significant effect of PXR on HNSCC cell growth, as evidenced in PXR knock-down experiments. PXR transcriptional activity is more importantly regulated by the presence of coactivators and corepressors than by PXR protein expression. To date, there is scarce information on the regulation of PXR in HNSCC and on its role in the pathogenesis of this disease. Coactivator and corepressor expression was screened through qRT-PCR in 8 HNSCC cell lines and correlated to PXR activity, determined by using a reporter gene assay. All cell lines considerably expressed all the cofactors assessed. PXR activity negatively correlated with nuclear receptor corepressor 2 (NCoR2) expression, indicating a major role of this corepressor in PXR modulation and suggesting its potential as a surrogate for PXR activity in HNSCC. To test the association of NCoR2 with the malignant phenotype, a subset of three cell lines was transfected with an over-expression plasmid for this corepressor. Subsequently, cell growth and chemoresistance assays were performed. To elucidate the mechanisms underlying NCoR2 effects on cell growth, caspase 3/7 activity and protein levels of cleaved caspase 3 and PARP were evaluated. In HNO97 cells, NCoR2 over-expression decreased cell growth, chemoresistance and increased cleaved caspase 3 levels, caspase activity and cleaved PARP levels. On the contrary, in HNO124 and HNO210 cells, NCoR2 over-expression increased cell growth, drug resistance and decreased cleaved caspase 3 levels, caspase activity and cleaved PARP levels. In conclusion, we demonstrated a role of PXR and NCoR2 in the modulation of cell growth in HNSCC. This may contribute to a better understanding of the highly variable HNSCC therapeutic response.

Indexed as

Cell ProliferationGene Expression Regulation, NeoplasticCarcinoma, Squamous CellCaspase 3Caspase 7Cell Line, TumorDrug Resistance, NeoplasmHead and Neck NeoplasmsHumansNeoplasm ProteinsNuclear Receptor Co-Repressor 2Pregnane X ReceptorReceptors, SteroidCASP3 protein, humanCASP7 protein, humanCaspase 3Caspase 7NCOR2 protein, humanNeoplasm ProteinsNuclear Receptor Co-Repressor 2Pregnane X ReceptorReceptors, Steroid

Identifiers

PMID29470550
PMCPMC5823449
OpenAlexW2788779464

What OpenQuestion holds

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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.