Evidence map›Paper›PMID 24490130›Full record

ArticleFEBS open bio2014

NFκB mediates cisplatin resistance through histone modifications in head and neck squamous cell carcinoma (HNSCC).

Luciana O Almeida, Aline C Abrahao, Luciana K Rosselli-Murai, Fernanda S Giudice, Chiara Zagni, Andreia M Leopoldino, Cristiane H Squarize, Rogerio M Castilho

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

Article in FEBS open bio, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
2.7field-weighted citation impact, top 11% 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

65 citing papers in PubMed, 111 citations in OpenAlex.

  1. Trial
  2. Head and neck squamous cell carcinoma: current and emerging therapeutic strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
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  19. Cephaeline is an inductor of histone H3 acetylation and inhibitor of mucoepidermoid carcinoma cancer stem cells.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2022
    Article
  20. Article

5 more citing papers are in PubMed but not listed here.

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 3 institutions in 2 countries.

Luciana O AlmeidaLaboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA ; Department of Clinical Analysis, Toxicology and Bromatology, School of Pharmacy, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
Aline C AbrahaoDepartment of Pathology and Oral Diagnosis, Federal University of Rio de Janeiro School of Dentistry, Rio de Janeiro, RJ, Brazil.
Luciana K Rosselli-MuraiLaboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
Fernanda S GiudiceLaboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
Chiara ZagniLaboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
Andreia M LeopoldinoDepartment of Clinical Analysis, Toxicology and Bromatology, School of Pharmacy, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
Cristiane H SquarizeLaboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
Rogerio M CastilhoLaboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
University of Michigan–Ann Arbor · USUniversidade de São Paulo · BRUniversidade Federal do Rio de Janeiro · BR

Funding

Therapeutic Potential and Mechanism of Action of Potent Small Molecule InhibitorsP50CA097248 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WOLF, GREGORY T · 2002 to 2013
$25.3M
NCI NIH HHS P50 CA097248
6 · The paper itself

Abstract

Cisplatin-based chemotherapy is the standard treatment of choice for head and neck squamous cell carcinoma (HNSCC). The efficiency of platinum-based therapies is directly influenced by the development of tumor resistance. Multiple signaling pathways have been linked to tumor resistance, including activation of nuclear factor kappa B (NFκB). We explore a novel mechanism by which NFκB drives HNSCC resistance through histone modifications. Post-translational modification of histones alters chromatin structure, facilitating the binding of nuclear factors that mediate DNA repair, transcription, and other processes. We found that chemoresistant HNSCC cells with active NFκB signaling respond to chemotherapy by reducing nuclear BRCA1 levels and by promoting histone deacetylation (chromatin compaction). Activation of this molecular signature resulted in impaired DNA damage repair, prolonged accumulation of histone γH2AX and increased genomic instability. We found that pharmacological induction of histone acetylation using HDAC inhibitors prevented NFκB-induced cisplatin resistance. Furthermore, silencing NFκB in HNSCC induced acetylation of tumor histones, resulting in reduced chemoresistance and increased cytotoxicity following cisplatin treatment. Collectively, these findings suggest that epigenetic modifications of HNSCC resulting from NFκB-induced histone modifications constitute a novel molecular mechanism responsible for chemoresistance in HNSCC. Therefore, targeted inhibition of HDAC may be used as a viable therapeutic strategy for disrupting tumor resistance caused by NFκB.

Indexed as

BRCA1, breast cancer type 1BSA, bovine serum albuminChemoresistanceChromatin remodelingDDR, DNA damage repairDMSO, dimethyl sulfoxideDSB, double strand breaksHDAC, histone deacetylasesHDAC inhibitorHistone acetylationHNSCCHNSCC, head and neck squamous cell carcinomaIC50, half maximal inhibitory concentrationIKKα, IκB kinase alphaIKKβ, IκB kinase betaMTS, non-radioactive cell proliferation assayNFκBNFκB, nuclear factor kappa BNIH, National Institutes of HealthsiRNA, small interfering RNATSA, trichostatin A

Identifiers

PMID24490130
PMCPMC3907686
OpenAlexW1964671531

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.