ArticleCancer science2014
Loss of hepatocyte growth factor activator inhibitor type 1 participates in metastatic spreading of human pancreatic cancer cells in a mouse orthotopic transplantation model.
Article in Cancer science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- The role of HAI-1 in urothelial bladder cancer: Tissue expression, ectodomain shedding and clinical outcomes.Biochemistry and biophysics reports · 2026Article
- Membrane-Anchored Serine Protease Inhibitors: Physiological Functions, Mechanisms, and Roles in Cancer.International journal of molecular sciences · 2026Review
- Biomimetic Tumour Model Systems for Pancreatic Ductal Adenocarcinoma in Relation to Photodynamic Therapy.International journal of molecular sciences · 2025Review
- Genetics of white color and iridophoroma in "Lemon Frost" leopard geckos.PLoS genetics · 2021Article
- Comprehensive Analysis of the Expression and Prognostic Value of SPINT1/2 in Breast Carcinoma.Frontiers in endocrinology · 2021Article
- Dysregulation of Type II Transmembrane Serine Proteases and Ligand-Dependent Activation of MET in Urological Cancers.International journal of molecular sciences · 2020Review
- Protease-activated receptor-2 accelerates intestinal tumor formation through activation of nuclear factor-κB signaling and tumor angiogenesis in ApcCancer science · 2020Article
- Entosis and apical cell extrusion constitute a tumor-suppressive mechanism downstream of Matriptase.The Journal of cell biology · 2020Article
- Zebrafish modeling reveals that SPINT1 regulates the aggressiveness of skin cutaneous melanoma and its crosstalk with tumor immune microenvironment.Journal of experimental & clinical cancer research : CR · 2019Article
- Cell surface-anchored serine proteases in cancer progression and metastasis.Cancer metastasis reviews · 2019Review
- Membrane-Anchored Serine Proteases and Protease-Activated Receptor-2-Mediated Signaling: Co-Conspirators in Cancer Progression.Cancer research · 2019Review
- Promoter Hypomethylation Is Responsible for Upregulated Expression of HAI-1 in Hepatocellular Carcinoma.Disease markers · 2019Article
- Engineering a potent inhibitor of matriptase from the natural hepatocyte growth factor activator inhibitor type-1 (HAI-1) protein.The Journal of biological chemistry · 2018Article
- Regulation of matriptase and HAI-1 system, a novel therapeutic target in human endometrial cancer cells.Oncotarget · 2018Article
- Hepatocyte growth factor activator inhibitor type-2 (HAI-2)/Oncotarget · 2018Article
- Increased expression of antisense lncRNAOncoTargets and therapy · 2018Article
- Prognostic significance of hepatocyte growth factor activator inhibitor type 1 (HAI-1) immunoreactivity in pancreatic ductal adenocarcinoma.BMC research notes · 2017Article
- Up-regulation of glycolysis promotes the stemness and EMT phenotypes in gemcitabine-resistant pancreatic cancer cells.Journal of cellular and molecular medicine · 2017Article
- Review
- Type II transmembrane serine proteases as potential targets for cancer therapy.Biological chemistry · 2016Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is a membrane-bound serine protease inhibitor that is expressed on the surface of epithelial and carcinoma cells. On the cell surface, HAI-1 regulates membrane-anchored serine proteases, with matriptase being the most critical target. Matriptase is involved in pericellular processing of biologically active molecules, including protease-activated receptor-2 (PAR-2). Previously we reported that S2-CP8 cells, a metastatic variant of the SUIT-2 human pancreatic adenocarcinoma cell line, showed markedly decreased HAI-1 expression. To assess the significance of HAI-1 loss in invasion and spontaneous metastasis of S2-CP8 cells, we established stable S2-CP8 sublines that expressed HAI-1 under the control of a tetracycline-regulated promoter. In vitro migration and invasion assays revealed inhibitory effects of HAI-1 on S2-CP8 cell migration and invasion. Matriptase activity was suppressed by the expression of HAI-1. As the enhanced invasiveness in the absence of HAI-1 was alleviated by knockdown of matriptase by 81% and of PAR-2 completely, and PAR-2 antagonist also suppressed the invasion, matriptase-mediated PAR-2 activation is involved in HAI-1 loss-induced invasion of S2-CP8 cells. We then analyzed the effect of HAI-1 expression on metastasis of S2-CP8 cells in vivo using a nude mouse orthotopic xenograft model. Although approximately 50% of the control mice developed distant metastasis, mice treated with doxycycline to induce HAI-1 expression did not develop metastasis. These data indicate that HAI-1 loss contributes to invasion and dissemination of a highly metastatic subline of SUIT-2, suggesting crucial roles for the balance of pericellular serine proteases/inhibitors in pancreatic cancer progression.
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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.