Document Detail

GI24 enhances tumor invasiveness by regulating cell surface membrane-type 1 matrix metalloproteinase.
MedLine Citation:
PMID:  20666777     Owner:  NLM     Status:  MEDLINE    
GI24, an immunoglobulin superfamily member, has been cloned from a placenta cDNA library as a gene product that promoted activation of matrix metalloproteinase (MMP)-2 mediated by membrane type (MT) 1-MMP. Co-expression of GI24 with MT1-MMP in HEK293T cells increased the cell-surface level of MT1-MMP concomitant with the cleavage of the GI24 at the juxtamembrane site to shed the extracellular domain. HT1080 fibrosarcoma cells stably transfected with the GI24 gene expressed a higher level of MT1-MMP and showed more invasive ability in collagen gel than the control cells. GI24 was cleaved in HT1080 cells, which was blocked by the administration of MMP inhibitor BB94 or transfection of small interfering RNA (siRNA) targeting MT1-MMP. GI24 expression is relatively high in some squamous carcinoma and hepatocarcinoma cell lines. Transfection of siRNA for GI24 into oral squamous carcinoma-derived HSC-4 cells, which express GI24 and MT1-MMP genes reduced the expression of not only GI24 but also MT1-MMP, and attenuated invasive growth in the collagen matrix. These results suggest that GI24 contributes to tumor-invasive growth in the collagen matrix by augmenting cell surface MT1-MMP.
Moustafa A Sakr; Takahisa Takino; Takahiro Domoto; Hiroshi Nakano; Richard W Wong; Motoko Sasaki; Yasuni Nakanuma; Hiroshi Sato
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cancer science     Volume:  101     ISSN:  1349-7006     ISO Abbreviation:  Cancer Sci.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-18     Completed Date:  2010-11-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101168776     Medline TA:  Cancer Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  2368-74     Citation Subset:  IM    
Copyright Information:
© 2010 Japanese Cancer Association.
Department of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
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MeSH Terms
Blotting, Western
Cell Line
Cell Line, Tumor
Cell Membrane / metabolism*
Collagen / metabolism
Enzyme Activation
Gene Library
Matrix Metalloproteinase 14 / antagonists & inhibitors,  genetics,  metabolism*
Matrix Metalloproteinase 2 / metabolism*
Membrane Proteins / genetics,  metabolism*
Phenylalanine / analogs & derivatives,  pharmacology
Placenta / metabolism
Protease Inhibitors / pharmacology
RNA Interference
Reverse Transcriptase Polymerase Chain Reaction
Thiophenes / pharmacology
Reg. No./Substance:
0/GI24 protein, human; 0/Membrane Proteins; 0/Protease Inhibitors; 0/Thiophenes; 130370-60-4/batimastat; 63-91-2/Phenylalanine; 9007-34-5/Collagen; EC Metalloproteinase 2; EC Metalloproteinase 14

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