Evidence map›Paper›PMID 31624299›Full record

ArticleCell death & disease2019

Loss of TIMP3 by promoter methylation of Sp1 binding site promotes oral cancer metastasis.

Chun-Wen Su, Yu-Chao Chang, Ming-Hsien Chien, Yi-Hsien Hsieh, Mu-Kuan Chen, Chiao-Wen Lin, Shun-Fa Yang

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
6.0field-weighted citation impact, top 3% 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

43 citing papers in PubMed, 88 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. The impact of long non-coding RNAJournal of Cancer · 2025
    Article
  6. International journal of medical sciences · 2025
    Article
  7. Long-Term Effect of TIMP3 Gene Expression on Thyroid Cancer: A Cure Model Analysis.Asian Pacific journal of cancer prevention : APJCP · 2024
    Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. The repertoire of mutational signatures in tobacco- and non-tobacco-induced oral cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023
    Review
  13. Review
  14. ZNF714 Supports Pro-Oncogenic Features in Lung Cancer Cells.International journal of molecular sciences · 2023
    Article
  15. Article
  16. Article
  17. Review
  18. The impact ofJournal of Cancer · 2023
    Article
  19. 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

7 authors at 4 institutions in 1 country.

Chun-Wen SuInstitute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Yu-Chao ChangSchool of Dentistry, Chung Shan Medical University, Taichung, Taiwan.
Ming-Hsien ChienGraduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.ORCID http://orcid.org/0000-0002-0084-7231
Yi-Hsien HsiehInstitute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan.
Mu-Kuan ChenInstitute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Chiao-Wen LinDepartment of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan. cwlin@csmu.edu.tw.
Shun-Fa YangInstitute of Medicine, Chung Shan Medical University, Taichung, Taiwan. ysf@csmu.edu.tw.ORCID http://orcid.org/0000-0002-0365-7927
Chung Shan Medical University Hospital · TWChanghua Christian Hospital · TWChung Shan Medical University · TWWan Fang Hospital · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The tissue inhibitor of metalloproteinase-3 (TIMP3) is the only member of the TIMP family that binds to the extracellular matrix and suppresses cancer cell growth, angiogenesis, migration, and invasion. However, whether the abnormal expression and promoter methylation of TIMP3 facilitates oral cancer metastasis remain unclear. In this study, the DNA methylation levels of TIMP3 CpG islands were assessed through pyrosequencing. Artificial modulation of TIMP3 was performed to explore the role of TIMP3 in tumor metastasis in vitro and in vivo. Our results showed that the suppression of TIMP3 transcription by DNA methylation involves the inhibition of the binding of the transcription factor Sp1 to the TIMP3 promoter as well as the upregulation of DNMT1 and DNMT3B. Functional analyses revealed that TIMP3 overexpression reduced migration and invasion abilities in oral cancer cells and inhibited lymph node metastasis in vivo. Moreover, TIMP3 regulated epithelial-mesenchymal transition by increasing the expression of the epithelial markers and reducing the expression of the mesenchymal markers. In conclusion, our findings suggested that the suppression of TIMP3 by DNA methylation contributes to oral cancer metastasis.

Indexed as

DNA MethylationAnimalsBinding SitesCell Line, TumorCpG IslandsHeterograftsHumansMaleMiceMice, SCIDMouth NeoplasmsNeoplasm MetastasisPromoter Regions, GeneticRNA, MessengerSp1 Transcription FactorSquamous Cell Carcinoma of Head and NeckRNA, MessengerSP1 protein, humanSp1 Transcription FactorTIMP3 protein, humanTissue Inhibitor of Metalloproteinase-3

Identifiers

PMID31624299
PMCPMC6797751
OpenAlexW2981037708

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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.