ArticleOncogene2014
HAI-2 suppresses the invasive growth and metastasis of prostate cancer through regulation of matriptase.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 68 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
- Engineered Expression of Hepatocyte Growth Factor Activator Inhibitor-1 (HAI-1) Reduces the Growth of Bladder Cancer Cells.Biomedicines · 2025Article
- Review
- Article
- Identifying feature genes of chickens with different feather pecking tendencies based on three machine learning algorithms and WGCNA.Frontiers in veterinary science · 2024Article
- 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
- A dual role for ERK-1/2 in the regulation of plasmin activity and cell migration in metastatic NSCLC-H1299 cells.Archives of toxicology · 2023Article
- Identification of blood protein biomarkers associated with prostate cancer risk using genetic prediction models: analysis of over 140,000 subjects.Human molecular genetics · 2023Article
- The serine protease matriptase inhibits migration and proliferation in multiple myeloma cells.Oncotarget · 2022Article
- Structure and activity of human TMPRSS2 protease implicated in SARS-CoV-2 activation.Nature chemical biology · 2022Article
- Environment-Sensitive Ectodomain Shedding of Epithin/PRSS14 Increases Metastatic Potential of Breast Cancer Cells by Producing CCL2.Molecules and cells · 2022Article
- Gene-associated methylation status of ST14 as a predictor of survival and hormone receptor positivity in breast Cancer.BMC cancer · 2021Article
- The Kunitz-type serine protease inhibitor Spint2 is required for cellular cohesion, coordinated cell migration and cell survival during zebrafish hatching gland development.Developmental biology · 2021Article
- Article
- A JUN N-terminal kinase inhibitor induces ectodomain shedding of the cancer-associated membrane protease Prss14/epithin via protein kinase CβII.The Journal of biological chemistry · 2020Article
- Dysregulation of Type II Transmembrane Serine Proteases and Ligand-Dependent Activation of MET in Urological Cancers.International journal of molecular sciences · 2020Review
- SPINT2 inhibits proteases involved in activation of both influenza viruses and metapneumoviruses.Virology · 2020Article
- Comprehensive review of targeted therapy for colorectal cancer.Signal transduction and targeted therapy · 2020Review
- Loss of SPINT2 expression frequently occurs in glioma, leading to increased growth and invasion via MMP2.Cellular oncology (Dordrecht, Netherlands) · 2020Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Dysregulation of cell surface proteolysis has been strongly implicated in tumorigenicity and metastasis. In this study, we delineated the role of hepatocyte growth factor activator inhibitor-2 (HAI-2) in prostate cancer (PCa) cell migration, invasion, tumorigenicity and metastasis using a human PCa progression model (103E, N1, and N2 cells) and xenograft models. N1 and N2 cells were established through serial intraprostatic propagation of 103E human PCa cells and isolation of the metastatic cells from nearby lymph nodes. The invasion capability of these cells was revealed to gradually increase throughout the serial isolations (103E<N1<N2). In this series of cells, the expression of HAI-2 but not HAI-1 was significantly decreased throughout the progression and occurred in parallel with increased activation of matriptase. The expression level and activity of matriptase increased whereas the HAI-2 protein level decreased over the course of orthotopic tumor growth in mice, which was consistent with the immunohistochemical profiles of matriptase and HAI-2 in archival PCa specimens. Knockdown of matriptase reduced the PCa cell invasion induced by HAI-2 knockdown. HAI-2 overexpression or matriptase silencing in N2 cells downregulated matriptase activity and significantly decreased tumorigenicity and metastatic capability in orthotopically xenografted mice. These results suggest that during the progression of human PCa, matriptase activity is primarily controlled by HAI-2 expression. The imbalance between HAI-2 and matriptase expression led to matriptase activation, thereby increasing cell migration, invasion, tumorigenicity and metastasis.
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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.