Evidence map›Paper›PMID 40764063›Full record

ArticleGut2026

Role of CNNM4 in the progression of cholangiocarcinoma: implications for ferroptosis and therapeutic potential.

Maria Mercado-Gómez, Naroa Goikoetxea-Usandizaga, Alvaro Eguileor Giné, Miguel A Merlos Rodrigo, Marta Bento Afonso, Mikel Azkargorta, Leidy Estefanía Zapata-Pavas, Claudia M Rejano-Gordillo, Marta R Romero, Isabel Mendizabal and 39 more

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Article in Gut, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
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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

49 authors.

Maria Mercado-Gómez *Liver Disease Lab, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain.ORCID 0000-0003-2765-6432
Naroa Goikoetxea-Usandizaga *Liver Disease Lab, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain.
Alvaro Eguileor GinéLiver Disease Lab, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain.
Miguel A Merlos RodrigoDepartment of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czech Republic.
Marta Bento AfonsoThe Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal.
Mikel AzkargortaProteomics Platform, Bizkaia Science and Technology Park, Derio, Spain.
Leidy Estefanía Zapata-PavasLiver Disease Lab, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain.
Claudia M Rejano-GordilloLiver Disease Lab, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain.
Marta R RomeroCenter for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain.
Isabel MendizabalCancer Cell Signaling and Metabolism Lab, CIC bioGUNE, Basque Research And Technology Alliance (BRTA), Derio, Spain.
Pedro M RodriguesCenter for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain.
Hanghang WuImmunology, Ophthalmology and ENT, Complutense University of Madrid Faculty of Medicine, Madrid, Comunidad de Madrid, Spain.
Rubén Rodríguez-AgudoLiver Disease Lab, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain.
Marina Serrano-MaciáLiver Disease Lab, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain.
Paula OlaizolaDepartment of Liver and Gastrointestinal Diseases, Biogipuzkoa Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), Donostia-San Sebastian, Spain.
Jon Ander Barrenechea-BarrenecheaLiver Disease Lab, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain.
Irene González RecioLiver Disease Lab, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain.
Maite G Fernandez-BarrenaCenter for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain.ORCID 0000-0003-0375-6236
Diletta OveriDepartment of Anatomical, Histological, Forensic Medicine and Orthopaedics Sciences, Sapienza University of Rome, Rome, Italy.ORCID 0000-0003-3561-8903
Eugenio GaudioDepartment of Anatomical, Histological, Forensic Medicine and Orthopaedics Sciences, Sapienza University of Rome, Rome, Italy.
Ute SchaeperSilenceTherapeutics GmbH, Berlin, Germany.
Saioa Garcia-LongarteCancer Cell Signaling and Metabolism Lab, CIC bioGUNE, Basque Research And Technology Alliance (BRTA), Derio, Spain.ORCID 0000-0001-5412-4234
Mariana Yáñez-BartoloméUpper Gastrointestinal and Endocrine Tumor Unit, VHIO, Vall d'Hebron University Hospital, Barcelona, Spain.
Patricia Peña-SanFelixLiver Disease Lab, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain.
Clàudia Gil-PitarchLiver Disease Lab, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain.
Ainhoa LapitzDepartment of Liver and Gastrointestinal Diseases, Biogipuzkoa Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), Donostia-San Sebastian, Spain.
Hana MichalkovaDepartment of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czech Republic.
Zbynek HegerDepartment of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czech Republic.
Carolina ConterLiver Disease Lab, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain.
Rocio I R MaciasCenter for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain.ORCID 0000-0002-4748-0326
Arkaitz CarracedoCancer Cell Signaling and Metabolism Lab, CIC bioGUNE, Basque Research And Technology Alliance (BRTA), Derio, Spain.
Jesús BañalesCenter for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain.
Victor MorenoSTART Madrid-FJD, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.ORCID 0000-0001-6099-4236
Angela LamarcaMedical Oncology, Fundacion Jimenez Diaz University Hospital, Madrid, Spain, Madrid, Spain.
Rajat SinghDepartment of Medicine, David Geffen School of Medicine, Los Angeles, California, USA.
Teresa Cardoso DelgadoLiver Disease Lab, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain.
Luis Alfonso Martínez-CruzLiver Disease Lab, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain.
Felix ElortzaProteomics Platform, CIC bioGUNE, ProteoRed-ISCIII, Bizkaia Science and Technology Park, Derio, Spain, CIC bioGUNE, Bizkaia, Spain.
Matias A AvilaCenter for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain.ORCID 0000-0001-6570-3557
César MartínBiochemistry and Molecular Biology, UPV/EHU, Leioa, Spain.
Tian V TianUpper Gastrointestinal and Endocrine Tumor Unit, VHIO, Vall d'Hebron University Hospital, Barcelona, Spain.ORCID 0000-0002-9906-0980
Teresa MacarullaUpper Gastrointestinal and Endocrine Tumor Unit, VHIO, Vall d'Hebron University Hospital, Barcelona, Spain.
Daniela BuccellaDepartment of Chemistry, New York University, New York, New York, USA.
Francisco Javier CuberoCenter for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain.ORCID 0000-0003-1499-650X
Diego F CalvisiInstitute of Pathology, University of Regensburg, Regensburg, Germany.
Guido CarpinoDepartment of Anatomical, Histological, Forensic Medicine and Orthopaedics Sciences, Sapienza University of Rome, Rome, Italy.ORCID 0000-0001-8570-2519
Jose J G MarinCenter for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid, Spain.ORCID 0000-0003-1186-6849
Cecília M P RodriguesThe Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal.
Maria Luz Martinez-ChantarLiver Disease Lab, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain mlmartinez@cicbiogune.es.ORCID 0000-0002-6446-9911

Funding

Molecular Probes Shed Light on Magnesium HomeostasisR01CA217817 · NCI · NEW YORK UNIVERSITY · PI BUCCELLA, DANIELA · 2017 to 2021
$1.7M
NCI NIH HHS R01 CA217817
6 · The paper itself

Abstract

BACKGROUND AND

objectiveCholangiocarcinoma (CCA) is a heterogeneous neoplasm of the biliary epithelium that easily infiltrates, metastasises and recurs. Magnesium disbalance is a hallmark of CCA, with the magnesium transporter cyclin M4 (CNNM4) being a key driver of various hepatic diseases. This study aims to unravel the role of CNNM4 in the initiation and progression of CCA.

designCNNM4 protein and gene expression were assessed in vitro, in vivo and in patients with CCA. Silencing of

resultsCNNM4 was upregulated in CCA samples from humans, mice and cell lines. Functional studies demonstrated that CNNM4 deficiency attenuates cell growth, chemoresistance, migration, invasion, cancer stem cell properties and Warburg effect in vitro and in vivo. Proteomic analysis identified nuclear protein 1 as an upstream regulator of CNNM4-induced ferroptosis in CCA, ultimately leading to cell death. The iron chelator deferiprone could reverse the decreased proliferation induced by

conclusionThis study reveals that increased CNNM4 expression drives CCA progression and malignancy and that its inhibition may be an effective therapeutic strategy to limit proliferation and metastasis in patients with CCA.

Indexed as

Bile Duct NeoplasmsCation Transport ProteinsCholangiocarcinomaFerroptosisAnimalsCell Line, TumorCell MovementCell ProliferationDisease ProgressionHumansMiceUp-RegulationCation Transport ProteinsCHOLANGIOCARCINOMAGENE THERAPYIRON METABOLISMREACTIVE OXYGEN SPECIES

Identifiers

PMID40764063
PMCPMC12911659

What OpenQuestion holds

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LicenceCC BY-NC
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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.