HAI-2 as a novel inhibitor of plasmin represses lung cancer cell invasion and metastasis.
Br J Cancer
; 120(5): 499-511, 2019 03.
Article
em En
| MEDLINE
| ID: mdl-30765871
ABSTRACT
BACKGROUND:
Dysregulation 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.METHODS:
Immunohistochemistry 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.RESULTS:
Hepatocyte 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-ß1, EMT and cell invasion. In addition, downregulated HAI-2 increased metastasis of lung adenocarcinoma via upregulating plasmin activity.CONCLUSION:
HAI-2 functions as a novel inhibitor of plasmin to suppress lung cancer cell motility, EMT and metastasis.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Glicoproteínas de Membrana
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Fibrinolisina
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Adenocarcinoma de Pulmão
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Neoplasias Pulmonares
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article