ArticleCancer discovery2014
The androgen-regulated protease TMPRSS2 activates a proteolytic cascade involving components of the tumor microenvironment and promotes prostate cancer metastasis.
Article in Cancer discovery, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 302 papers, 2 of them syntheses that pooled it.
What it found
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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
302 citing papers in PubMed, 2 syntheses or guidelines pooled it, 488 citations in OpenAlex.
- Pooled it
- Polymorphism of tmprss2 (rs12329760) but not ace2 (rs4240157), tmprss11a (rs353163) and cd147 (rs8259) is associated with the severity of COVID-19 in the Ukrainian population.Acta bio-medica : Atenei Parmensis · 2023Pooled it
- Temporal dynamics of the immune response to neoadjuvant androgen deprivation therapy suggest a window of opportunity for checkpoint inhibitor therapy in prostate cancer.Journal for immunotherapy of cancer · 2026Article
- New determinant of influenza hemagglutinin cleavability identified through random mutagenesis for acid-stabilizing mutations.Microbiology spectrum · 2026Article
- Lock out: targeting TMPRSS2 to block influenza and coronaviruses.Journal of virology · 2026Review
- Computational Analysis of Iron-binding Proteins in the Mutational Landscape of Cancer.Biological trace element research · 2026Article
- COVID-19 Prophylactic Effect of Bromhexine Hydrochloride.Immunity, inflammation and disease · 2026Article
- Expression of angiotensin-converting enzyme 2, transmembrane serine protease 2, and sirtuin 1 proteins in lungs of different age groups.Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia · 2026Article
- Efficient production of fully active, SARS-CoV-2-priming, wildtype TMPRSS2 ectodomain via co-expression of HAI-2 allows for both auto- and cross-activation mechanisms.The Biochemical journal · 2025Article
- First real-world evidence from the Emilia-Romagna region suggests tamoxifen protects breast cancer patients from COVID-19.Scientific reports · 2025Article
- Dexamethasone enhances intestinal glucose absorption and TMPRSS2 expression with implications for hyperglycaemia and infection risk.Scientific reports · 2025Article
- Increased ErbB2 Signaling Is an Early Adaptation to Androgen Signaling Inhibition and Persists in Castration-Resistant Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Prognostic Role of Prostate-Specific Antigen (PSA) in male patients hospitalized for COVID-19.Pakistan journal of medical sciences · 2025Article
- Review
- Article
- Simulations and active learning enable efficient identification of an experimentally-validated broad coronavirus inhibitor.Nature communications · 2025Article
- The crystal structure of coronavirus RBD-TMPRSS2 complex provides basis for the discovery of therapeutic antibodies.Nature communications · 2025Article
- Effects and regulation of ACE2 and TMPRSS2 abundance in healthy humans and in patients with SARS-CoV-2.Biochemical Society transactions · 2025Article
- From N-0385 to N-0920: Unveiling a Host-Directed Protease Inhibitor with Picomolar Antiviral Efficacy against Prevalent SARS-CoV-2 Variants.Journal of medicinal chemistry · 2025Article
- CRISPR-Cas9 genetic screens reveal regulation of TMPRSS2 by the Elongin BC-VHL complex.Scientific reports · 2025Article
242 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 2 institutions in 2 countries.
Funding
Abstract
unlabelledTMPRSS2 is an androgen-regulated cell-surface serine protease expressed predominantly in prostate epithelium. TMPRSS2 is expressed highly in localized high-grade prostate cancers and in the majority of human prostate cancer metastases. Through the generation of mouse models with a targeted deletion of Tmprss2, we demonstrate that the activity of this protease regulates cancer cell invasion and metastasis to distant organs. By screening combinatorial peptide libraries, we identified a spectrum of TMPRSS2 substrates that include pro-hepatocyte growth factor (HGF). HGF activated by TMPRSS2 promoted c-MET receptor tyrosine kinase signaling, and initiated a proinvasive epithelial-to-mesenchymal transition phenotype. Chemical library screens identified a potent bioavailable TMPRSS2 inhibitor that suppressed prostate cancer metastasis in vivo. Together, these findings provide a mechanistic link between androgen-regulated signaling programs and prostate cancer metastasis that operate via context-dependent interactions with extracellular constituents of the tumor microenvironment. SIGNIFICANCE: The vast majority of prostate cancer deaths are due to metastasis. Loss of TMPRSS2 activity dramatically attenuated the metastatic phenotype through mechanisms involving the HGF-c-MET axis. Therapeutic approaches directed toward inhibiting TMPRSS2 may reduce the incidence or progression of metastasis in patients with prostate cancer.
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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.