ArticleOncogene2020
Inhibition of TMPRSS2 by HAI-2 reduces prostate cancer cell invasion and metastasis.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 46 citations in OpenAlex.
- Hepatocyte growth factor activator inhibitor-2 rapidly inactivates airway-expressed human type II transmembrane serine proteases.The Journal of biological chemistry · 2026Article
- Membrane-Anchored Serine Protease Inhibitors: Physiological Functions, Mechanisms, and Roles in Cancer.International journal of molecular sciences · 2026Review
- 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
- Myeloid-Derived Growth Factor-Regulated Oncogenesis in Lung Adenocarcinoma Is Associated with EGFR Status and Cancer Aggressiveness.Journal of proteome research · 2025Article
- SPINT1 Expressed in Epithelial Cells of Choroid Plexus in Human and Mouse Brains.International journal of molecular sciences · 2025Article
- Bridging Cancer and COVID-19: The Complex Interplay of ACE2 and TMPRSS2.Cancer medicine · 2025Review
- Review
- Resolving the Structure of a Guanine Quadruplex in TMPRSS2 Messenger RNA by Circular Dichroism and Molecular Modeling.Chemistry (Weinheim an der Bergstrasse, Germany) · 2024Article
- Article
- Menin in Cancer.Genes · 2024Review
- The Inhibition of Serine Proteases by Serpins Is Augmented by Negatively Charged Heparin: A Concise Review of Some Clinically Relevant Interactions.International journal of molecular sciences · 2024Review
- Biomarkers for Diagnosing and Treating Fetal Growth Restriction.Current medicinal chemistry · 2024Review
- SPINT2 is involved in the proliferation, migration and phenotypic switching of aortic smooth muscle cells: Implications for the pathogenesis of thoracic aortic dissection.Experimental and therapeutic medicine · 2023Article
- Unravelling the Role of P300 and TMPRSS2 in Prostate Cancer: A Literature Review.International journal of molecular sciences · 2023Review
- PM2.5 promotes lung cancer progression through activation of the AhR-TMPRSS2-IL18 pathway.EMBO molecular medicine · 2023Article
- SARS-CoV-2 and gastrointestinal diseases.Frontiers in microbiology · 2023Review
- Structure and activity of human TMPRSS2 protease implicated in SARS-CoV-2 activation.Nature chemical biology · 2022Article
- Transmembrane Protease Serine 2 Proteolytic Cleavage of the SARS-CoV-2 Spike Protein: A Mechanistic Quantum Mechanics/Molecular Mechanics Study to Inspire the Design of New Drugs To Fight the COVID-19 Pandemic.Journal of chemical information and modeling · 2022Article
- Review
- Nanoparticles for Coronavirus Control.Nanomaterials (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TMPRSS2 is an important membrane-anchored serine protease involved in human prostate cancer progression and metastasis. A serine protease physiologically often comes together with a cognate inhibitor for execution of proteolytically biologic function; however, TMPRSS2's cognate inhibitor is still elusive. To identify the cognate inhibitor of TMPRSS2, in this study, we applied co-immunoprecipitation and LC/MS/MS analysis and isolated hepatocyte growth factor activator inhibitors (HAIs) to be potential inhibitor candidates for TMPRSS2. Moreover, the recombinant HAI-2 proteins exhibited a better inhibitory effect on TMPRSS2 proteolytic activity than HAI-1, and recombinant HAI-2 proteins had a high affinity to form a complex with TMPRSS2. The immunofluorescence images further showed that TMPRSS2 was co-localized to HAI-2. Both KD1 and KD2 domain of HAI-2 showed comparable inhibitory effects on TMPRSS2 proteolytic activity. In addition, HAI-2 overexpression could suppress the induction effect of TMPRSS2 on pro-HGF activation, extracellular matrix degradation and prostate cancer cell invasion. We further determined that the expression levels of TMPRSS2 were inversely correlated with HAI-2 levels during prostate cancer progression. In orthotopic xenograft animal model, TMPRSS2 overexpression promoted prostate cancer metastasis, and HAI-2 overexpression efficiently blocked TMPRSS2-induced metastasis. In summary, the results together indicate that HAI-2 can function as a cognate inhibitor for TMPRSS2 in human prostate cancer cells and may serve as a potential factor to suppress TMPRSS2-mediated malignancy.
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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.