論文 - 詳細
| RRC ID | 42652 |
|---|---|
| 著者 | Takeuchi T, Adachi Y, Sonobe H, Furihata M, Ohtsuki Y. |
| タイトル | A ubiquitin ligase, skeletrophin, is a negative regulator of melanoma invasion. |
| ジャーナル | Oncogene |
| Abstract |
Skeletrophin (mindbomb homolog 2 (MIB2)) is a RING (Really Interesting New Gene) finger-dependent ubiquitin ligase, which targets the intracellular region of Notch ligands. A previous immunohistochemical study demonstrated that skeletrophin was downregulated in many melanomas. In the present study, we have identified a promoter region of skeletrophin on a CpG island and detected aberrant methylation of this region in six of 31 invasive melanomas, but in none of 25 benign nevi or five non-invasive superficial spreading melanomas. Subsequently, we found that a zinc-finger transcriptional factor Snail, which is overexpressed in many melanoma cells, repressed the skeletrophin promoter activity via an E-box-related element and was involved in downregulation of skeletrophin. An activator protein-2, which has a tumor suppressor-like role in melanoma, increased skeletrophin expression. Interestingly, exogenously expressed skeletrophin reduced melanoma cell invasion in vitro and in vivo. Colony formation in soft agar was also reduced in a RING motif-dependent manner, without affecting cell growth. We also found that skeletrophin downregulated transcription of the Met oncogene, which encodes the hepatocyte growth factor receptor and plays a role in the determination of the invasive phenotype of many malignant tumors. Finally, exogenously expressed skeletrophin, but not its RING mutant, increased transcription of Hes1 gene, a downstream effector of Notch pathway in melanoma cells. The present findings indicate that skeletrophin might be a novel suppressor factor for melanoma invasion. |
| 巻・号 | 25(53) |
| ページ | 7059-69 |
| 公開日 | 2006-11-9 |
| DOI | 10.1038/sj.onc.1209688 |
| PII | 1209688 |
| PMID | 16715130 |
| MeSH | Animals Cell Line Chlorocebus aethiops CpG Islands Gene Expression Regulation, Neoplastic Homeodomain Proteins / genetics Humans Melanoma / enzymology* Melanoma / genetics Melanoma / pathology* Methylation Mice Mice, Nude Molecular Sequence Data Neoplasm Invasiveness / genetics Neoplasm Invasiveness / pathology Neoplastic Stem Cells Promoter Regions, Genetic Proto-Oncogene Proteins c-met / genetics RNA, Messenger / genetics Snail Family Transcription Factors Transcription Factor AP-2 / genetics Transcription Factor AP-2 / metabolism Transcription Factors / genetics Transcription Factors / metabolism Ubiquitin-Protein Ligases / genetics Ubiquitin-Protein Ligases / metabolism* Xenograft Model Antitumor Assays |
| IF | 7.971 |
| 引用数 | 28 |
| WOS 分野 | GENETICS & HEREDITY ONCOLOGY BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | COLO 679(RCB0989) 293(RCB1637) |