A LIN28B-RAN-AURKA Signaling Network Promotes Neuroblastoma Tumorigenesis.
Cancer Cell
; 28(5): 599-609, 2015 Nov 09.
Article
em En
| MEDLINE
| ID: mdl-26481147
ABSTRACT
A more complete understanding of aberrant oncogenic signaling in neuroblastoma, a malignancy of the developing sympathetic nervous system, is paramount to improving patient outcomes. Recently, we identified LIN28B as an oncogenic driver in high-risk neuroblastoma. Here, we identify the oncogene RAN as a LIN28B target and show regional gain of chromosome 12q24 as an additional somatic alteration resulting in increased RAN expression. We show that LIN28B influences RAN expression by promoting RAN Binding Protein 2 expression and by directly binding RAN mRNA. Further, we demonstrate a convergence of LIN28B and RAN signaling on Aurora kinase A activity. Collectively, these findings demonstrate that LIN28B-RAN-AURKA signaling drives neuroblastoma oncogenesis, suggesting that this pathway may be amenable to therapeutic targeting.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Proteínas de Ligação a RNA
/
Proteína ran de Ligação ao GTP
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Aurora Quinase A
/
Neuroblastoma
Tipo de estudo:
Prognostic_studies
Limite:
Child
/
Humans
Idioma:
En
Revista:
Cancer Cell
Ano de publicação:
2015
Tipo de documento:
Article