論文 - 詳細
| RRC ID | 45254 |
|---|---|
| 著者 | Solari V, Borriello L, Turcatel G, Shimada H, Sposto R, Fernandez GE, Asgharzadeh S, Yates EA, Turnbull JE, DeClerck YA. |
| タイトル | MYCN-dependent expression of sulfatase-2 regulates neuroblastoma cell survival. |
| ジャーナル | Cancer Res |
| Abstract |
Heparan sulfate proteoglycans (HSPG) play a critical role in the interaction of tumor cells and their microenvironment. HSPG activity is dictated by sulfation patterns controlled by sulfotransferases, which add sulfate groups, and sulfatases (Sulf), which remove 6-O-sulfates. Here, we report altered expression of these enzymes in human neuroblastoma cells with higher levels of Sulf-2 expression, a specific feature of MYCN-amplified cells (MYCN-A cells) that represent a particularly aggressive subclass. Sulf-2 overexpression in neuroblastoma cells lacking MYCN amplification (MYCN-NA cells) increased their in vitro survival. Mechanistic investigations revealed evidence of a link between Sulf-2 expression and MYCN pathogenicity in vitro and in vivo. Analysis of Sulf-2 protein expression in 65 human neuroblastoma tumors demonstrated a higher level of Sulf-2 expression in MYCN-A tumors than in MYCN-NA tumors. In two different patient cohorts, we confirmed the association in expression patterns of Sulf-2 and MYCN and determined that Sulf-2 overexpression predicted poor outcomes in a nonindependent manner with MYCN. Our findings define Sulf-2 as a novel positive regulator of neuroblastoma pathogenicity that contributes to MYCN oncogenicity. Cancer Res; 74(21); 5999-6009. ©2014 AACR. |
| 巻・号 | 74(21) |
| ページ | 5999-6009 |
| 公開日 | 2014-11-1 |
| DOI | 10.1158/0008-5472.CAN-13-2513 |
| PII | 0008-5472.CAN-13-2513 |
| PMID | 25164011 |
| PMC | PMC4216758 |
| MeSH | Cell Line, Tumor Cell Survival Gene Expression Regulation, Neoplastic Heparan Sulfate Proteoglycans / metabolism* Humans N-Myc Proto-Oncogene Protein Neuroblastoma / genetics* Neuroblastoma / pathology Nuclear Proteins / genetics Nuclear Proteins / metabolism* Oncogene Proteins / genetics Oncogene Proteins / metabolism* Signal Transduction / genetics Sulfatases Sulfotransferases / biosynthesis* Sulfotransferases / genetics Tumor Microenvironment / genetics |
| IF | 9.727 |
| 引用数 | 8 |
| WOS 分野 | ONCOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 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 | NB19(RCB0479) |