Evidence map›Paper›PMID 40564959›Full record

ArticleInternational journal of molecular sciences2025

Transglutaminase 2 Stimulates Cell Proliferation and Modulates Transforming Growth Factor-Beta Signaling Pathway Independently of Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma Cells.

Hiromi Yamaguchi, Ramiro José González-Duarte, Xian-Yang Qin, Yuriko Abe, Ichiro Takada, Benjamin Charroy, Verna Cázares-Ordoñez, Shigeyuki Uno, Makoto Makishima, Mariko Esumi

Abstract read
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In one paragraph

Article in International journal of molecular sciences, 2025. 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
  2. Article
  3. 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

10 authors.

Hiromi YamaguchiDivision of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo 173-8610, Japan.
Ramiro José González-DuarteDivision of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo 173-8610, Japan.ORCID 0000-0002-6041-9888
Xian-Yang QinLaboratory for Cellular Function Conversion Technology, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.ORCID 0000-0002-0110-6849
Yuriko AbeDivision of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo 173-8610, Japan.
Ichiro TakadaDivision of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo 173-8610, Japan.
Benjamin CharroyDivision of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo 173-8610, Japan.
Verna Cázares-OrdoñezDivision of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo 173-8610, Japan.ORCID 0000-0003-3564-0369
Shigeyuki UnoDivision of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo 173-8610, Japan.
Makoto MakishimaDivision of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo 173-8610, Japan.ORCID 0000-0002-4630-905X
Mariko EsumiDivision of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo 173-8610, Japan.ORCID 0000-0002-4253-2027

Funding

JSPS KAKENHI JP18K15102
6 · The paper itself

Abstract

Transglutaminase 2 (TG2) is a multifunctional protein and plays a role in cancer progression. We previously identified TG2 as an early-recurrence biomarker in hepatocellular carcinoma (HCC). TG2-knockdown (shTG2) and control (shCtl) HCC cell lines were used for comparative analyses to clarify the molecular mechanisms underlying the contribution of this protein to HCC malignancy. The proliferation of shTG2 cells was slightly but significantly decreased compared with that of shCtl cells. Differential gene expression profiling based on GeneChip arrays revealed the enrichment of the PI3K-Akt signaling pathway and showed that the expression of Dickkopf-1 and -3 (DKK1 and DKK3, respectively), inhibitors and modulators of the Wnt/β-catenin signaling pathway, was increased in shTG2 cells. The expression of epithelial-mesenchymal transition (EMT)-related genes was similar in both shCtl and shTG2 cells before and after TGF-β1 treatment, even though TGF-β1 markedly upregulated TG2. Thus, TG2 may contribute to cancer malignancy via the stimulation of cell proliferation signaling, such as PI3K-Akt and Wnt/β-catenin signaling, but not EMT. This effect might be further enhanced by humoral factors such as TGF-β1 from the tumor microenvironment.

Indexed as

Carcinoma, HepatocellularEpithelial-Mesenchymal TransitionGTP-Binding ProteinsLiver NeoplasmsTransforming Growth Factor betaTransforming Growth Factor beta1TransglutaminasesAdaptor Proteins, Signal TransducingCell Line, TumorCell ProliferationGene Expression Regulation, NeoplasticHumansIntercellular Signaling Peptides and ProteinsPhosphatidylinositol 3-KinasesProtein Glutamine gamma Glutamyltransferase 2Proto-Oncogene Proteins c-aktAdaptor Proteins, Signal TransducingDKK1 protein, humanDKK3 protein, humanGTP-Binding ProteinsIntercellular Signaling Peptides and ProteinsPhosphatidylinositol 3-KinasesProtein Glutamine gamma Glutamyltransferase 2Proto-Oncogene Proteins c-aktTransforming Growth Factor betaTransforming Growth Factor beta1Transglutaminasesepithelial–mesenchymal transitionhepatocellular carcinomaPI3K-Akt signalingTGF-β1transglutaminase 2tumor microenvironmentWnt/β-catenin signaling

Identifiers

PMID40564959
PMCPMC12192954

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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.