ArticleCancer science2011
Hepatocyte growth factor activator inhibitor type 1 suppresses metastatic pulmonary colonization of pancreatic carcinoma cells.
Article in Cancer science, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Membrane-Anchored Serine Protease Inhibitors: Physiological Functions, Mechanisms, and Roles in Cancer.International journal of molecular sciences · 2026Review
- Usability Evaluation of Urinary HAI-1, STMN-1 and TN-C in the Diagnosis of Bladder Cancer.Journal of clinical medicine · 2025Article
- Insufficiency of hepatocyte growth factor activator inhibitor-1 confers lymphatic invasion of tongue carcinoma cells.Cancer science · 2022Article
- Dysregulation of Type II Transmembrane Serine Proteases and Ligand-Dependent Activation of MET in Urological Cancers.International journal of molecular sciences · 2020Review
- A bi-specific inhibitor targeting IL-17A and MMP-9 reduces invasion and motility in MDA-MB-231 cells.Oncotarget · 2018Article
- 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
- Investigation into metastatic processes and the therapeutic effects of gemcitabine on human pancreatic cancer using an orthotopic SUIT-2 pancreatic cancer mouse model.Oncology letters · 2018Article
- Hepatocyte growth factor activator inhibitor type-2 (HAI-2)/Oncotarget · 2018Article
- Prognostic significance of hepatocyte growth factor activator inhibitor type 1 (HAI-1) immunoreactivity in pancreatic ductal adenocarcinoma.BMC research notes · 2017Article
- Recent advances on plasmin inhibitors for the treatment of fibrinolysis-related disorders.Medicinal research reviews · 2014Review
- Review
- Loss of hepatocyte growth factor activator inhibitor type 1 participates in metastatic spreading of human pancreatic cancer cells in a mouse orthotopic transplantation model.Cancer science · 2014Article
- Down-regulation of HAI-1 is associated with poor-differentiation status of colorectal cancer.Human cell · 2013Article
- Regulation of pericellular proteolysis by hepatocyte growth factor activator inhibitor type 1 (HAI-1) in trophoblast cells.Human cell · 2012Article
- Membrane-bound serine protease inhibitor HAI-1 is required for maintenance of intestinal epithelial integrity.The American journal of pathology · 2011Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is a transmembrane protease inhibitor that regulates the activities of membrane-bound and extracellular serine proteases. HAI-1 has two Kunitz-type inhibitor domains with the N-terminal Kunitz domain (KD1) responsible for inhibiting known target proteases. Previously, we reported that knockdown of HAI-1 in the human pancreatic carcinoma cell line SUIT-2 resulted in epithelial to mesenchymal transition. To evaluate the role of HAI-1 in metastasis, we examined the metastatic capability of SUIT-2 cells that did or did not stably express HAI-1 short-hairpin RNA in an experimental pulmonary metastasis assay using nude mice. The extent of pulmonary metastasis was verified by histological examination and direct measurement of human cytokeratin 19 mRNA levels. One week after injecting SUIT-2 cells into mouse tail veins, apparent metastatic colonization was observed in 36% (4/11) of mice injected with HAI-1-knockdown SUIT-2, whereas none (0/11) of the control mice were positive for metastasis. After 2 weeks the metastasis positive ratios were 80% (4/5) and 40% (2/5), and after 4 weeks the ratios were 82% (9/11) and 45% (5/11) for HAI-1-knockdown and control SUIT-2 cells, respectively. Thus, loss of HAI-1 promoted pulmonary metastasis. Co-injection of recombinant KD1 abolished metastasis produced by HAI-1-knockdown SUIT-2 cells after 1 week. Moreover, recombinant KD1 restored E-cadherin levels in HAI-1 knockdown SUIT-2 cells and reduced their invasiveness in vitro. These data indicate that HAI-1 regulates pulmonary metastasis of SUIT-2, and KD1 may have therapeutic application for inhibiting metastatic cancer cell spreading.
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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.