Evidence map›Paper›PMID 35418692›Full record

ArticleOncogene2022

Matriptase-2/NR4A3 axis switches TGF-β action toward suppression of prostate cancer cell invasion, tumor growth, and metastasis.

Hsin-Ying Lin, Chun-Jung Ko, Tzu-Yu Lo, Shang-Ru Wu, Shao-Wei Lan, Chen-An Huang, Yi-Chin Lin, Hsin-Hsien Lin, Hsin-Fang Tu, Cheng-Fan Lee and 5 more

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.1field-weighted citation impact, top 26% 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

8 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. NNMT-mediated NOncogene · 2025
    Article
  3. Review
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  5. Article
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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

15 authors at 4 institutions in 1 country.

Hsin-Ying LinDepartment of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.ORCID http://orcid.org/0000-0001-8851-2964
Chun-Jung KoDepartment of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.ORCID http://orcid.org/0000-0001-6565-7060
Tzu-Yu LoDepartment of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.ORCID http://orcid.org/0000-0002-9101-8550
Shang-Ru WuDepartment of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.ORCID http://orcid.org/0000-0002-3018-4213
Shao-Wei LanDepartment of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
Chen-An HuangDepartment of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
Yi-Chin LinDepartment of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
Hsin-Hsien LinDepartment of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
Hsin-Fang TuDepartment of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
Cheng-Fan LeeDepartment of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
Pei-Wen HsiaoAgricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan, ROC.ORCID http://orcid.org/0000-0002-3589-6754
Hsiang-Po HuangGraduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.ORCID http://orcid.org/0000-0002-3382-305X
Mei-Jou ChenDepartment of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan, ROC.
Kai-Hsiung ChangInstitute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan, ROC.
Ming-Shyue LeeDepartment of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC. mslee2006@ntu.edu.tw.ORCID http://orcid.org/0000-0002-8673-5088
National Taiwan University · TWAgricultural Biotechnology Research Center, Academia Sinica · TWNational Health Research Institutes · TWNational Taiwan University Hospital · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dysregulation of pericellular proteolysis is strongly implicated in cancer metastasis through alteration of cell invasion and the microenvironment. Matriptase-2 (MT-2) is a membrane-anchored serine protease which can suppress prostate cancer (PCa) cell invasion. In this study, we showed that MT-2 was down-regulated in PCa and could suppress PCa cell motility, tumor growth, and metastasis. Using microarray and biochemical analysis, we found that MT-2 shifted TGF-β action towards its tumor suppressor function by repressing epithelial-to-mesenchymal transition (EMT) and promoting Smad2 phosphorylation and nuclear accumulation to upregulate two TGF-β1 downstream effectors (p21 and PAI-1), culminating in hindrance of PCa cell motility and malignant growth. Mechanistically, MT-2 could dramatically up-regulate the expression of nuclear receptor NR4A3 via iron metabolism in PCa cells. MT-2-induced NR4A3 further coactivated Smad2 to activate p21 and PAI-1 expression. In addition, NR4A3 functioned as a suppressor of PCa and mediated MT-2 signaling to inhibit PCa tumorigenesis and metastasis. These results together indicate that NR4A3 sustains MT-2 signaling to suppress PCa cell invasion, tumor growth, and metastasis, and serves as a contextual factor for the TGF-β/Smad2 signaling pathway in favor of tumor suppression via promoting p21 and PAI-1 expression.

Indexed as

DNA-Binding ProteinsMembrane ProteinsProstatic NeoplasmsReceptors, SteroidReceptors, Thyroid HormoneSerine EndopeptidasesCell Line, TumorCell MovementEpithelial-Mesenchymal TransitionHumansMaleNeoplasm InvasivenessPlasminogen Activator Inhibitor 1ProstateTransforming Growth Factor beta1Tumor MicroenvironmentDNA-Binding Proteinsmatriptase 2Membrane ProteinsNR4A3 protein, humanPlasminogen Activator Inhibitor 1Receptors, SteroidReceptors, Thyroid HormoneSerine EndopeptidasesTransforming Growth Factor beta1

Identifiers

PMID35418692
OpenAlexW4223657151

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.