GREB1 induced by Wnt signaling promotes development of hepatoblastoma by suppressing TGFß signaling.
Nat Commun
; 10(1): 3882, 2019 08 28.
Article
en En
| MEDLINE
| ID: mdl-31462641
ABSTRACT
The ß-catenin mutation is frequently observed in hepatoblastoma (HB), but the underlying mechanism by which Wnt/ß-catenin signaling induces HB tumor formation is unknown. Here we show that expression of growth regulation by estrogen in breast cancer 1 (GREB1) depends on Wnt/ß-catenin signaling in HB patients. GREB1 is localized to the nucleus where it binds Smad2/3 in a competitive manner with p300 and inhibits TGFß signaling, thereby promoting HepG2 HB cell proliferation. Forced expression of ß-catenin, YAP, and c-Met induces HB-like mouse liver tumor (BYM mice), with an increase in GREB1 expression and HB markers. Depletion of GREB1 strongly suppresses marker gene expression and HB-like liver tumorigenesis, and instead enhances TGFß signaling in BYM mice. Furthermore, antisense oligonucleotides for GREB1 suppress the formation of HepG2 cell-induced tumors and HB-like tumors in vivo. We propose that GREB1 is a target molecule of Wnt/ß-catenin signaling and required for HB progression.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factor de Crecimiento Transformador beta
/
Hepatoblastoma
/
Vía de Señalización Wnt
/
Neoplasias Hepáticas
/
Proteínas de Neoplasias
Límite:
Adolescent
/
Animals
/
Child
/
Child, preschool
/
Humans
/
Infant
/
Male
/
Newborn
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Japón