Metadherin-PRMT5 complex enhances the metastasis of hepatocellular carcinoma through the WNT-ß-catenin signaling pathway.
Carcinogenesis
; 41(2): 130-138, 2020 04 22.
Article
em En
| MEDLINE
| ID: mdl-31498866
ABSTRACT
Accumulating data suggest that metadherin (MTDH) may function as an oncogene. Our previous study showed that MTDH promotes hepatocellular carcinoma (HCC) metastasis via the epithelial-mesenchymal transition. In this study, we aim to further elucidate how MTDH promotes HCC metastasis. Using Co-immunoprecipitation (co-IP) and mass spectrometry, we found that MTDH can specifically bind to protein arginine methyltransferase 5 (PRMT5). Further functional assays revealed that PRMT5 overexpression promoted the proliferation and motility of HCC cells and that knockout of PRMT5 impeded the effect of MTDH. The immunohistochemistry assay/tissue microarray results showed that when MTDH was overexpressed in HCC cells, PRMT5 translocated from the nucleus to the cytoplasm, with the subsequent translocation of ß-catenin from the cytoplasm to the nucleus and upregulation of the WNT-ß-catenin signaling pathway. Further in vivo experiments suggested that PRMT5 and ß-catenin played a pivotal role in MTDH-mediated HCC metastasis. We therefore concluded that the MTDH-PRMT5 complex promotes HCC metastasis by regulating the WNT-ß-catenin signaling pathway.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteína-Arginina N-Metiltransferases
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Proteínas de Ligação a RNA
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Carcinoma Hepatocelular
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Via de Sinalização Wnt
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Neoplasias Hepáticas
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Proteínas de Membrana
Limite:
Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article