| RRC ID |
57639
|
| 著者 |
Matsumoto S, Yamamichi T, Shinzawa K, Kasahara Y, Nojima S, Kodama T, Obika S, Takehara T, Morii E, Okuyama H, Kikuchi A.
|
| タイトル |
GREB1 induced by Wnt signaling promotes development of hepatoblastoma by suppressing TGFβ signaling.
|
| ジャーナル |
Nat Commun
|
| Abstract |
The β-catenin mutation is frequently observed in hepatoblastoma (HB), but the underlying mechanism by which Wnt/β-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/β-catenin signaling in HB patients. GREB1 is localized to the nucleus where it binds Smad2/3 in a competitive manner with p300 and inhibits TGFβ signaling, thereby promoting HepG2 HB cell proliferation. Forced expression of β-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 TGFβ 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/β-catenin signaling and required for HB progression.
|
| 巻・号 |
10(1)
|
| ページ |
3882
|
| 公開日 |
2019-8-28
|
| DOI |
10.1038/s41467-019-11533-x
|
| PII |
10.1038/s41467-019-11533-x
|
| PMID |
31462641
|
| PMC |
PMC6713762
|
| MeSH |
Adolescent
Animals
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use
Carcinogenesis
Cell Line, Tumor
Cell Proliferation
Child
Child, Preschool
Gene Expression Regulation, Neoplastic
Hepatoblastoma / genetics
Hepatoblastoma / metabolism*
Humans
Infant
Infant, Newborn
Liver Neoplasms / genetics
Liver Neoplasms / metabolism*
Liver Neoplasms / pathology
Male
Mice
Mice, Nude
Molecular Targeted Therapy
Neoplasm Proteins / genetics*
Neoplasm Proteins / metabolism
Neoplasm Transplantation
Oligonucleotides, Antisense / pharmacology
Oligonucleotides, Antisense / therapeutic use
Transforming Growth Factor beta / metabolism*
Wnt Signaling Pathway*
beta Catenin / metabolism
|
| IF |
12.121
|
| 引用数 |
3
|
| リソース情報 |
| 遺伝子材料 |
CSII-CMV-MCS-IRES2-Bsd (RDB04385)
pCMV-VSV-G-RSV-Rev (RDB04393)
pCAG-HIVgp (RDB04394) |
