Evidence map›Paper›PMID 41823075›Full record

ArticleLiver international : official journal of the International Association for the Study of the Liver2026

Trefoil Factor-3 Is a Hypoxia-Triggered Pro-Tumorigenic Factor in Hepatoblastoma.

Luz A Martínez-Pérez, M Ujue Latasa, Iker Uriarte, Amaya López-Pascual, Jasmin Elurbide, Pavel Strnad, Sona Frankova, Eva Sticova, Ondrej Fabian, Maria Arechederra and 16 more

Abstract read
In one paragraph

Article in Liver international : official journal of the International Association for the Study of the Liver, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Trefoil Factor-3 Is a Hypoxia-Triggered Pro-Tumorigenic Factor in Hepatoblastoma.Liver international : official journal of the International Association for the Study of the Liver · 2026
    Article
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

26 authors.

Luz A Martínez-PérezDepartamento de Ciencias de la Salud, Centro Universitarios de los Altos, Universidad de Guadalajara, Tepatitlán, México.
M Ujue LatasaHepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain.
Iker UriarteHepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain.ORCID 0000-0001-5237-7799
Amaya López-PascualHepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain.
Jasmin ElurbideHepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain.
Pavel StrnadMedical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany.
Sona FrankovaDepartment of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Eva SticovaDepartment of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Ondrej FabianDepartment of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Maria ArechederraHepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain.
Eva SantamariaCIBERehd, Madrid, Spain.
Josepmaria ArgemiInstituto de Investigaciones Sanitarias de Navarra IdiSNA, Pamplona, Spain.
Bruno SangroInstituto de Investigaciones Sanitarias de Navarra IdiSNA, Pamplona, Spain.
Beatrice FogliaDepartment Clinical and Biological Sciences, Unit of Experimental Medicine and Clinical Pathology, University of Torino, Torino, Italy.
Maurizio ParolaDepartment Clinical and Biological Sciences, Unit of Experimental Medicine and Clinical Pathology, University of Torino, Torino, Italy.
Melva Gutiérrez-AnguloDepartamento de Ciencias de la Salud, Centro Universitarios de los Altos, Universidad de Guadalajara, Tepatitlán, México.
Stefano CairoChampions Oncology, Rockville, Maryland, USA.
Ramón BatallerCIBERehd, Madrid, Spain.
Pau Sancho-BruCIBERehd, Madrid, Spain.
Maria L Martinez-ChantarCIBERehd, Madrid, Spain.ORCID 0000-0002-6446-9911
Jose J G MarinCIBERehd, Madrid, Spain.ORCID 0000-0003-1186-6849
Andrea CastanedaChildhood Liver Oncology Group, Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain.
Carolina ArmengolCIBERehd, Madrid, Spain.
Carmen BerasainHepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain.ORCID 0000-0001-7075-2476
Maite G Fernandez-BarrenaHepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain.
Matias A ÁvilaHepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain.ORCID 0000-0001-6570-3557

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND &

aimsHepatoblastoma (HB) is the most common malignant liver tumour in children. Despite improved survival in low-risk disease, outcomes for advanced or relapsed HB remain poor, emphasising the need for new therapeutic targets. Hypoxia, a hallmark of aggressive tumours, has recently been implicated in HB pathogenesis, but the molecular mechanisms involved are unclear. This study aimed to characterise the hypoxia-driven transcriptomic landscape of HB and identify key mediators of tumour progression.

methodsTranscriptomic analyses of HB cell lines cultured under normoxic and hypoxic conditions were combined with bioinformatic interrogation of public HB datasets, immunohistochemistry of human and murine tumours and plasma ELISA assays. Functional roles of trefoil factor 3 (TFF3) were evaluated through overexpression and shRNA-mediated knockdown in vitro and in a β-catenin/YAP-driven mouse model of HB.

resultsHypoxia induced broad transcriptional reprogramming in HB cells, including significant upregulation of TFF3, a secreted oncogenic peptide. TFF3 expression was elevated in HB tissues and plasma, and colocalized with hypoxia marker carbonic anhydrase 9 (CA9). TFF3 promoted proliferation, anchorage-independent growth and cisplatin resistance under both normoxia and hypoxia. Knockdown of murine Tff3 suppressed tumour formation and angiogenesis in vivo. Transcriptomic and molecular analyses revealed that TFF3 sustains C-MYC expression and modulates mTOR/GSK3β signalling.

conclusionsTFF3 is a hypoxia-inducible factor that enhances HB cell proliferation, survival and chemoresistance. Its tumour-promoting activity through C-MYC and mTOR pathways identifies TFF3 as a potential therapeutic target and circulating biomarker in hepatoblastoma.

Indexed as

HepatoblastomaLiver NeoplasmsTrefoil Factor-3AnimalsCell Line, TumorCell ProliferationGene Expression Regulation, NeoplasticGlycogen Synthase Kinase 3 betaHumansHypoxiaMiceSignal TransductionGlycogen Synthase Kinase 3 betaTFF3 protein, humanTrefoil Factor-3biomarkerscarcinogenesishepatoblastomahypoxiatrefoil factors

Identifiers

PMID41823075
PMCPMC12983189

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.