ArticleBritish journal of cancer2019
HAI-2 as a novel inhibitor of plasmin represses lung cancer cell invasion and metastasis.
Article in British journal of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- SerpinB7 promotes c-Myc-mediated glycolysis by interacting with ANXA2 to facilitate the progression of non-small cell lung cancer.Molecular cancer · 2026Article
- Membrane-Anchored Serine Protease Inhibitors: Physiological Functions, Mechanisms, and Roles in Cancer.International journal of molecular sciences · 2026Review
- Study of non-surgical therapeutic patterns and prognosis in elderly patients with stage II non-small-cell lung cancer: an investigational study based on the SEER database.Translational cancer research · 2025Article
- 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
- 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
- TRPM7 restrains plasmin activity and promotes transforming growth factor-β1 signaling in primary human lung fibroblasts.Archives of toxicology · 2022Article
- 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
- SPINT2 inhibits proteases involved in activation of both influenza viruses and metapneumoviruses.Virology · 2020Article
- Loss of SPINT2 expression frequently occurs in glioma, leading to increased growth and invasion via MMP2.Cellular oncology (Dordrecht, Netherlands) · 2020Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDysregulation of pericellular proteolysis usually accounts for cancer cell invasion and metastasis. Isolation of a cell-surface protease system for lung cancer metastasis is an important issue for mechanistic studies and therapeutic target identification.
methodsImmunohistochemistry of a tissue array (n = 64) and TCGA database (n = 255) were employed to assess the correlation between serine protease inhibitors (SPIs) and lung adenocarcinoma progression. The role of SPI in cell motility was examined using transwell assays. Pulldown and LC/MS/MS were performed to identify the SPI-modulated novel protease(s). A xenografted mouse model was harnessed to demonstrate the role of the SPI in lung cancer metastasis.
resultsHepatocyte growth factor activator inhibitor-2 (HAI-2) was identified to be downregulated following lung cancer progression, which was related to poor survival and tumour invasion. We further isolated a serum-derived serine protease, plasmin, to be a novel target of HAI-2. Downregulation of HAI-2 promotes cell surface plasmin activity, EMT, and cell motility. HAI-2 can suppress plasmin-mediated activations of HGF and TGF-β1, EMT and cell invasion. In addition, downregulated HAI-2 increased metastasis of lung adenocarcinoma via upregulating plasmin activity.
conclusionHAI-2 functions as a novel inhibitor of plasmin to suppress lung cancer cell motility, EMT and metastasis.
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