論文 - 詳細
| RRC ID | 35154 |
|---|---|
| 著者 | Ylivinkka I, Hu Y, Chen P, Rantanen V, Hautaniemi S, Nyman TA, Keski-Oja J, Hyytiäinen M. |
| タイトル | Netrin-1-induced activation of Notch signaling mediates glioblastoma cell invasion. |
| ジャーナル | J Cell Sci |
| Abstract |
Glioblastoma multiforme is an aggressively invasive human brain cancer, which lacks effective treatment. The axonal guidance protein, netrin-1, is overexpressed in glioblastoma tumor biopsies. In Matrigel invasion assays we observed that experimental overexpression of netrin-1 increased cell invasiveness and its downregulation decreased invasiveness. Using tandem affinity purification and mass spectrometry protein identification we found that netrin-1 forms a complex with both Notch2 and Jagged1. Recombinant netrin-1 colocalized with Jagged1 and Notch2 at the cell surface and was also present in the intracellular vesicles with Jagged1, but not with Notch2. Netrin-1 activated Notch signaling and subsequent glioblastoma cell invasion. Interestingly, the recombinant central domain of netrin-1 counteracted the effects of the full-length netrin-1: it inhibited glioblastoma cell invasion and Notch activation by retaining the Notch signaling complex at the cell surface. This finding may give rise to therapeutic applications. These results reveal a new mechanism leading to glioblastoma cell invasion, in which netrin-1 activates Notch signaling. |
| 巻・号 | 126(Pt 11) |
| ページ | 2459-69 |
| 公開日 | 2013-6-1 |
| DOI | 10.1242/jcs.120022 |
| PII | jcs.120022 |
| PMID | 23549787 |
| MeSH | Calcium-Binding Proteins / genetics Calcium-Binding Proteins / metabolism* Cell Line, Tumor Glioblastoma / drug therapy Glioblastoma / genetics Glioblastoma / metabolism* Glioblastoma / pathology Humans Intercellular Signaling Peptides and Proteins / genetics Intercellular Signaling Peptides and Proteins / metabolism* Jagged-1 Protein Membrane Proteins / genetics Membrane Proteins / metabolism* Neoplasm Invasiveness Nerve Growth Factors / genetics Nerve Growth Factors / metabolism* Nerve Growth Factors / pharmacology Netrin-1 Protein Structure, Tertiary Receptor, Notch2 / genetics Receptor, Notch2 / metabolism* Recombinant Proteins / genetics Recombinant Proteins / metabolism Recombinant Proteins / pharmacology Serrate-Jagged Proteins Signal Transduction* Tumor Suppressor Proteins / genetics Tumor Suppressor Proteins / metabolism* Tumor Suppressor Proteins / pharmacology |
| IF | 4.573 |
| 引用数 | 13 |
| WOS 分野 | CELL BIOLOGY |
| リソース情報 | |
| 遺伝子材料 | pEF-BOSneoSE-mNotch2 RAMIC (RDB06772) |