Frizzled2 signaling regulates growth of high-risk neuroblastomas by interfering with ß-catenin-dependent and ß-catenin-independent signaling pathways.
Oncotarget
; 7(29): 46187-46202, 2016 Jul 19.
Article
de En
| MEDLINE
| ID: mdl-27323822
ABSTRACT
Frizzled2 (FZD2) is a receptor for Wnts and may activate both canonical and non-canonical Wnt signaling pathways in cancer. However, no studies have reported an association between FZD2 signaling and high-risk NB so far. Here we report that FZD2 signaling pathways are critical to NB growth in MYCN-single copy SK-N-AS and MYCN-amplified SK-N-DZ high-risk NB cells. We demonstrate that stimulation of FZD2 by Wnt3a and Wnt5a regulates ß-catenin-dependent and -independent Wnt signaling factors. FZD2 blockade suppressed ß-catenin-dependent signaling activity and increased phosphorylation of PKC, AKT and ERK in vitro, consistent with upregulation of ß-catenin-independent signaling activity. Finally, FZD2 small interfering RNA knockdown suppressed tumor growth in murine NB xenograft models associated with suppressed ß-catenin-dependent signaling and a less vascularized phenotype in both NB xenografts. Together, our study suggests a role for FZD2 in high-risk NB cell growth and provides a potential candidate for therapeutic inhibition in FZD2-expressing NB patients.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Récepteurs Frizzled
/
Voie de signalisation Wnt
/
Neuroblastome
Type d'étude:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limites:
Animals
/
Humans
Langue:
En
Journal:
Oncotarget
Année:
2016
Type de document:
Article
Pays d'affiliation:
Autriche