ArticleCancer science2015
Methylation-induced downregulation of TFPI-2 causes TMPRSS4 overexpression and contributes to oncogenesis in a subset of non-small-cell lung carcinoma.
Article in Cancer science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- TMPRSS4 as an emerging potential poor prognostic factor for solid tumors: A systematic review and meta-analysis.Oncotarget · 2016Pooled it
- TFPI2 in tumor metastasis: a double-edged sword with clinical implications.Cancer biology & therapy · 2026Review
- Reassessing the Role of Tissue Factor Pathway Inhibitor 2 in Neoplastic and Non-Neoplastic Lesions.Cancers · 2025Review
- Tissue factor pathway inhibitor-2 (TFPI-2)-an underappreciated partaker in cancer and metastasis.Cancer metastasis reviews · 2024Review
- Integrative analyses of RNA-seq and ChIP-seq Reveal MITF as a Target Gene of TFPI-2 in MDA231 Cells.Biochemical genetics · 2023Article
- TMPRSS4, a type II transmembrane serine protease, as a potential therapeutic target in cancer.Experimental & molecular medicine · 2023Review
- Identifying General Tumor and Specific Lung Cancer Biomarkers by Transcriptomic Analysis.Biology · 2022Article
- Preparation of FA-targeted magnetic nanocomposites co-loading TFPI-2 plasmid and cis-platinum and its targeted therapy effects on nasopharyngeal carcinoma.International journal of medical sciences · 2021Article
- The upregulation of TMPRSS4, partly ascribed to the downregulation of miR‑125a‑5p, promotes the growth of human lung adenocarcinoma via the NF‑κB signaling pathway.International journal of oncology · 2018Article
- TMPRSS4 Upregulates TWIST1 Expression through STAT3 Activation to Induce Prostate Cancer Cell Migration.Pathology oncology research : POR · 2018Article
- Cell-surface marker discovery for lung cancer.Oncotarget · 2017Article
- [Effects of decitabine on proliferation capacity and TFPI-2 expression in leukemia K562 cells].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2017Article
- Overexpression of TMPRSS4 promotes tumor proliferation and aggressiveness in breast cancer.International journal of molecular medicine · 2017Article
- Tissue factor pathway inhibitor-2 induced hepatocellular carcinoma cell differentiation.Saudi journal of biological sciences · 2017Article
- Type II transmembrane serine proteases as potential targets for cancer therapy.Biological chemistry · 2016Review
- Epigenetic alterations leading to TMPRSS4 promoter hypomethylation and protein overexpression predict poor prognosis in squamous lung cancer patients.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We identified transmembrane protease, serine 4 (TMPRSS4) as a putative, druggable target by screening surgically resected samples from 90 Japanese non-small-cell lung cancer (NSCLC) patients using cDNA microarray. TMPRSS4 has two druggable domains and was upregulated in 94.5% of the lung cancer specimens. Interestingly, we found that TMPRSS4 expression was associated with tissue factor pathway inhibitor 2 (TFPI-2) expression in these clinical samples. In contrast to TMPRSS4, TFPI-2 expression was downregulated in NSCLC samples. The in vitro induction of TFPI-2 in lung cancer cell lines decreased the expression of TMPRSS4 mRNA levels. Reporter assay showed that TFPI-2 inhibited transcription of TMPRSS4, although partially. Knockdown of TMPRSS4 reduced the proliferation rate in several lung cancer cell lines. When lung cancer cell lines were treated with 5-aza-2'-deoxycytidine or trichostatin A, their proliferation rate and TMPRSS4 mRNA expression levels were also reduced through the upregulation of TFPI-2 by decreasing its methylation in vitro. The TFPI-2 methylation level in the low TMPRSS4 group appeared to be significantly low in NSCLC samples (P = 0.02). We found a novel molecular mechanism that TFPI-2 negatively regulates cell growth by inhibiting transcription of TMPRSS4. We suggest that TMPRSS4 is upregulated by silencing of TFPI-2 through aberrant DNA methylation and contributes to oncogenesis in NSCLC.
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