ArticleScientific reports2019
Identification of a novel synthetic lethal vulnerability in non-small cell lung cancer by co-targeting TMPRSS4 and DDR1.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Pooled it
- Discoidin Domain Receptors in Tumor Biology and Immunology: Progression and Challenge.Biomolecules · 2025Review
- TFAP2C-DDR1 axis regulates resistance to CDK4/6 inhibitor in breast cancer.Cancer letters · 2025Article
- DDR1 as a key prognostic biomarker in non-small cell lung cancer: identification, validation, and potential therapeutic implications.Frontiers in immunology · 2025Article
- Review
- TMPRSS4, a type II transmembrane serine protease, as a potential therapeutic target in cancer.Experimental & molecular medicine · 2023Review
- Integration of bioinformatics analysis and experimental validation identifies plasma exosomal miR-103b/877-5p/29c-5p as diagnostic biomarkers for early lung adenocarcinoma.Cancer medicine · 2022Article
- Article
- Genetic and pharmacological tools to study the role of discoidin domain receptors in kidney disease.Frontiers in pharmacology · 2022Review
- A novel DDR1 inhibitor enhances the anticancer activity of gemcitabine in pancreatic cancer.American journal of cancer research · 2022Article
- Article
- The Yin and Yang of Discoidin Domain Receptors (DDRs): Implications in Tumor Growth and Metastasis Development.Cancers · 2021Review
- Inhibition of DDR1 enhances in vivo chemosensitivity in KRAS-mutant lung adenocarcinoma.JCI insight · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Finding novel targets in non-small cell lung cancer (NSCLC) is highly needed and identification of synthetic lethality between two genes is a new approach to target NSCLC. We previously found that TMPRSS4 promotes NSCLC growth and constitutes a prognostic biomarker. Here, through large-scale analyses across 5 public databases we identified consistent co-expression between TMPRSS4 and DDR1. Similar to TMPRSS4, DDR1 promoter was hypomethylated in NSCLC in 3 independent cohorts and hypomethylation was an independent prognostic factor of disease-free survival. Treatment with 5-azacitidine increased DDR1 levels in cell lines, suggesting an epigenetic regulation. Cells lacking TMPRSS4 were highly sensitive to the cytotoxic effect of the DDR1 inhibitor dasatinib. TMPRSS4/DDR1 double knock-down (KD) cells, but not single KD cells suffered a G0/G1 cell cycle arrest with loss of E2F1 and cyclins A and B, increased p21 levels and a larger number of cells in apoptosis. Moreover, double KD cells were highly sensitized to cisplatin, which caused massive apoptosis (~40%). In vivo studies demonstrated tumor regression in double KD-injected mice. In conclusion, we have identified a novel vulnerability in NSCLC resulting from a synthetic lethal interaction between DDR1 and TMPRSS4.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.