| RRC ID |
45254
|
| Author |
Solari V, Borriello L, Turcatel G, Shimada H, Sposto R, Fernandez GE, Asgharzadeh S, Yates EA, Turnbull JE, DeClerck YA.
|
| Title |
MYCN-dependent expression of sulfatase-2 regulates neuroblastoma cell survival.
|
| Journal |
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.
|
| Volume |
74(21)
|
| Pages |
5999-6009
|
| Published |
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
|
| Times Cited |
8
|
|
WOS Category
|
ONCOLOGY
|
| Resource |
| Human and Animal Cells |
NB19(RCB0479) |
