Reference - Detail
| RRC ID | 57639 |
|---|---|
| Author | Matsumoto S, Yamamichi T, Shinzawa K, Kasahara Y, Nojima S, Kodama T, Obika S, Takehara T, Morii E, Okuyama H, Kikuchi A. |
| Title | GREB1 induced by Wnt signaling promotes development of hepatoblastoma by suppressing TGFβ signaling. |
| Journal | 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. |
| Volume | 10(1) |
| Pages | 3882 |
| Published | 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 |
| Times Cited | 3 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | News |
| Total number of mentions | 14 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| DNA material | CSII-CMV-MCS-IRES2-Bsd (RDB04385) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394) |