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 Sulfotransferases / biosynthesis* Sulfotransferases / genetics Tumor Microenvironment / genetics
IF 8.378
Times Cited 4
Human and Animal Cells