| Cleavage of Hepatocyte Growth Factor Activator Inhibitor-1 by Membrane-Type MMP-1 Activates Matriptase. | |
| | |
MedLine Citation:
|
PMID: 22118498 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Co-expression of membrane-type matrix metalloproteinase-1 (MT1-MMP) with hepatocyte growth factor (HGF) activator inhibitor-1 (HAI-1) in HEK293T cells resulted in cleavage of HAI-1 to produce 3 fragments. Recombinant MT1-MMP was shown to cleave HAI-1 protein in vitro. HAI-1 was initially identified as the cognate inhibitor of matriptase, which is a transmembrane serine protease and processes urokinase-type plasminogen activator (uPA). Co-expression of HAI-1 with matriptase suppressed matriptase protease activity, and co-expression of MT1-MMP with them resulted in recovery of matriptase activity by stimulating shedding of HAI-1 fragments. Matriptase protein was detected in squamous carcinoma-derived HSC-4 cells, however, matriptase protease activity was undetectable. Transfection of small interfering RNA (siRNA) for HAI-1 enhanced serine protease activity, which was suppressed by co-transfection of matriptase siRNA. Collagen-gel culture or treatment with Concanavalin A (ConA) of HSC-4 cells enhanced MT1-MMP activity, which induced shedding of HAI-1 fragments and conversely stimulated uPA activation by these cells. Serine protease activity including uPA activation of cells treated with ConA was abrogated by down-regulation of either matriptase or MT1-MMP through the transfection of each siRNA. These results suggest that MT1-MMP induced by collagen-gel culture or ConA treatment causes cleavage and shedding of HAI-1 protein, which allows activation of matriptase in HSC-4 cells. HSC-4 cells showed a characteristic invasive growth by forming vacuole-like structures in collagen gel, which was suppressed by transfection of siRNA for either MT1-MMP or matriptase, suggesting that activation of matriptase through the cleavage of HAI-1 is one of the MT1-MMP multifunctions essential for invasive growth of HSC-4 cells. |
| | |
Authors:
|
Takahiro Domoto; Takahisa Takino; Luyang Guo; Hiroshi Sato |
Related Documents
:
|
21769428 - Redistribution of dr4 and dr5 in lipid rafts accounts for the sensitivity to trail in n... 22007388 - Cell-cycle-dependent variations in the ftir spectroscopy of hela cells treated with tri... 22256858 - Molecular characteristics and alterations during early development of the human vagina. 1009448 - Principal cells in lateral geniculate: effects of metrazol on capacity to after-discharge. 21368128 - Grazer cues induce stealth behavior in marine dinoflagellates. 6831408 - Protection against heat-induced cell killing by polyols in vitro. |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-11-26 |
Journal Detail:
|
Title: Cancer science Volume: - ISSN: 1349-7006 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
|
Created Date: 2011-11-28 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 101168776 Medline TA: Cancer Sci Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
|
© 2011 Japanese Cancer Association. |
Affiliation:
|
Department of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Long-term survival in patients with non-small cell lung cancer and synchronous brain metastasis trea...
Next Document: Modulating the structure and properties of poly(sodium 4-styrenesulfonate)/poly(diallyldimethylammon...