ECD promotes gastric cancer metastasis by blocking E3 ligase ZFP91-mediated hnRNP F ubiquitination and degradation.
Cell Death Dis
; 9(5): 479, 2018 05 01.
Article
em En
| MEDLINE
| ID: mdl-29706618
ABSTRACT
The human ortholog of the Drosophila ecdysoneless gene (ECD) is required for embryonic development and cell-cycle progression; however, its role in cancer progression and metastasis remains unclear. Here, we found that ECD is frequently overexpressed in gastric cancer (GC), especially in metastatic GC, and is correlated with poor clinical outcomes in GC patients. Silencing ECD inhibited GC migration and invasion in vitro and metastasis in vivo, while ECD overexpression promoted GC migration and invasion. ECD promoted GC invasion and metastasis by protecting hnRNP F from ubiquitination and degradation. We identified ZFP91 as the E3 ubiquitin ligase that is responsible for hnRNP F ubiquitination at Lys 185 and proteasomal degradation. ECD competitively bound to hnRNP F via the N-terminal STG1 domain (13-383aa), preventing hnRNP F from interacting with ZFP91, thus preventing ZFP91-mediated hnRNP F ubiquitination and proteasomal degradation. Collectively, our findings indicate that ECD promotes cancer invasion and metastasis by preventing E3 ligase ZFP91-mediated hnRNP F ubiquitination and degradation, suggesting that ECD may be a marker for poor prognosis and a potential therapeutic target for GC patients.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
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Proteínas de Transporte
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Movimento Celular
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Ribonucleoproteínas Nucleares Heterogêneas Grupo F-H
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Ubiquitina-Proteína Ligases
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Ubiquitinação
Tipo de estudo:
Prognostic_studies
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:
2018
Tipo de documento:
Article