Evidence map›Paper›PMID 37620936›Full record

ArticleJournal of biomedical science2023

5'-Ectonucleotidase CD73/NT5E supports EGFR-mediated invasion of HPV-negative head and neck carcinoma cells.

Enxian Shi, Zhengquan Wu, Birnur Sinem Karaoglan, Sabina Schwenk-Zieger, Gisela Kranz, Nilofer Abdul Razak, Christoph A Reichel, Martin Canis, Philipp Baumeister, Reinhard Zeidler and 1 more

Open access · diamondAbstract read
In one paragraph

Article in Journal of biomedical science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.8field-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

14 citing papers in PubMed, 12 citations in OpenAlex.

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  13. Bioinformatics analysis revealsTranslational cancer research · 2024
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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 1 institution in 1 country.

Enxian Shi *Department of Otorhinolaryngology, Head and Neck Surgery, LMU University Hospital, LMU Munich, Munich, Germany.
Zhengquan Wu *Department of Otorhinolaryngology, Head and Neck Surgery, LMU University Hospital, LMU Munich, Munich, Germany.
Birnur Sinem KaraoglanDepartment of Otorhinolaryngology, Head and Neck Surgery, LMU University Hospital, LMU Munich, Munich, Germany.
Sabina Schwenk-ZiegerDepartment of Otorhinolaryngology, Head and Neck Surgery, LMU University Hospital, LMU Munich, Munich, Germany.
Gisela KranzDepartment of Otorhinolaryngology, Head and Neck Surgery, LMU University Hospital, LMU Munich, Munich, Germany.
Nilofer Abdul RazakDepartment of Otorhinolaryngology, Head and Neck Surgery, LMU University Hospital, LMU Munich, Munich, Germany.
Christoph A ReichelDepartment of Otorhinolaryngology, Head and Neck Surgery, LMU University Hospital, LMU Munich, Munich, Germany.
Martin CanisDepartment of Otorhinolaryngology, Head and Neck Surgery, LMU University Hospital, LMU Munich, Munich, Germany.
Philipp BaumeisterDepartment of Otorhinolaryngology, Head and Neck Surgery, LMU University Hospital, LMU Munich, Munich, Germany.
Reinhard ZeidlerDepartment of Otorhinolaryngology, Head and Neck Surgery, LMU University Hospital, LMU Munich, Munich, Germany.
Olivier GiresDepartment of Otorhinolaryngology, Head and Neck Surgery, LMU University Hospital, LMU Munich, Munich, Germany. olivier.gires@med.uni-muenchen.de.ORCID http://orcid.org/0000-0002-2292-7064
LMU Klinikum · DE

Funding

Deutsches Forschungszentrum für Gesundheit und Umwelt, Helmholtz Zentrum München Intramural Funding
6 · The paper itself

Abstract

backgroundEpithelial-to-mesenchymal transition (EMT) of malignant cells is a driving force of disease progression in human papillomavirus-negative (HPV-negative) head and neck squamous cell carcinomas (HNSCC). Sustained hyper-activation of epidermal growth factor receptor (EGFR) induces an invasion-promoting subtype of EMT (EGFR-EMT) characterized by a gene signature ("'EGFR-EMT_Signature'") comprising 5´-ectonucleotidase CD73. Generally, CD73 promotes immune evasion via adenosine (ADO) formation and associates with EMT and metastases. However, CD73 regulation through EGFR signaling remains under-explored and targeting options are amiss.

methodsCD73 functions in EGFR-mediated tumor cell dissemination were addressed in 2D and 3D cellular models of migration and invasion. The novel antagonizing antibody 22E6 and therapeutic antibody Cetuximab served as inhibitors of CD73 and EGFR, respectively, in combinatorial treatment. Specificity for CD73 and its role as effector or regulator of EGFR-EMT were assessed upon CD73 knock-down and over-expression. CD73 correlation to tumor budding was studied in an in-house primary HNSCC cohort. Expression correlations, and prognostic and predictive values were analyzed using machine learning-based algorithms and Kaplan-Meier survival curves in single cell and bulk RNA sequencing datasets.

resultsCD73/NT5E is induced by the EGF/EGFR-EMT-axis and blocked by Cetuximab and MEK inhibitor. Inhibition of CD73 with the novel antagonizing antibody 22E6 specifically repressed EGFR-dependent migration and invasion of HNSCC cells in 2D. Cetuximab and 22E6 alone reduced local invasion in a 3D-model. Interestingly, combining inefficient low-dose concentrations of Cetuximab and 22E6 revealed highly potent in invasion inhibition, substantially reducing the functional IC

conclusionsIn sum, CD73 is an effector of EGF/EGFR-mediated local invasion and a potential therapeutic target and candidate predictive marker for advanced HPV-negative HNSCC.

Indexed as

5'-NucleotidaseGPI-Linked ProteinsHead and Neck NeoplasmsPapillomavirus InfectionsSquamous Cell Carcinoma of Head and NeckCetuximabEpidermal Growth FactorErbB ReceptorsHumans5'-NucleotidaseCetuximabEGFR protein, humanEpidermal Growth FactorErbB ReceptorsGPI-Linked ProteinsNT5E protein, humanAntagonistic antibodyCD73EGFREMTHNSCCInvasion

Identifiers

PMID37620936
PMCPMC10463398
OpenAlexW4386141932

What OpenQuestion holds

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LicenceCC BY
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.