Reference - Detail
| RRC ID | 42044 |
|---|---|
| Author | Ueda J, Kajita M, Suenaga N, Fujii K, Seiki M. |
| Title | Sequence-specific silencing of MT1-MMP expression suppresses tumor cell migration and invasion: importance of MT1-MMP as a therapeutic target for invasive tumors. |
| Journal | Oncogene |
| Abstract |
Membrane-type 1 matrix metalloproteinase (MT1-MMP/MMP-14) has been believed a key enzyme in tumor invasion, because it is expressed in a variety of malignant human tumors, and overexpression of the enzyme enhances the ability of cellular invasiveness. However, it has not necessarily been clarified whether the endogenously expressed MT1-MMP in human tumors plays a critical role in their invasiveness. We used RNA silencing technology to downregulate the endogenous MT1-MMP expression in human tumor cells (fibrosarcoma HT1080 and gastric carcinoma MKN-28 cell lines), and evaluated the effect on the invasion of a reconstituted basement membrane (Matrigel). Transfection of a double-stranded RNA targeted to the MT1-MMP gene decreased the level of the enzyme to less than 10-20% without affecting production of other MMPs. According to the degree of silencing, activation of proMMP-2 was inhibited. CD44 shedding was also inhibited, but only in part. Decreased MT1-MMP levels were also reflected in reduced cell motility on hyaluronan (HA) and invasion in Matrigel. Thus, specific downregulation of MT1-MMP expression was sufficient to cause significant inhibition of the migration and invasion of tumor cells, even though other MMPs continued to be expressed. |
| Volume | 22(54) |
| Pages | 8716-22 |
| Published | 2003-11-27 |
| DOI | 10.1038/sj.onc.1206962 |
| PII | 1206962 |
| PMID | 14647466 |
| MeSH | Cell Line, Tumor Cell Movement Enzyme Activation Enzyme Precursors / metabolism Gelatinases / metabolism Gene Silencing* Humans Hyaluronan Receptors / physiology Matrix Metalloproteinases, Membrane-Associated Metalloendopeptidases / antagonists & inhibitors* Metalloendopeptidases / genetics Metalloendopeptidases / metabolism Metalloendopeptidases / physiology Neoplasm Invasiveness Neoplasms / therapy* RNA, Double-Stranded / physiology RNA, Messenger / analysis Stomach Neoplasms / pathology |
| IF | 7.971 |
| Times Cited | 110 |
| WOS Category | GENETICS & HEREDITY ONCOLOGY BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | MKN28(RCB1000) |