Upregulation of the GRIM-19 gene suppresses invasion and metastasis of human gastric cancer SGC-7901 cell line.
Exp Cell Res
; 316(13): 2061-70, 2010 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-20478305
ABSTRACT
Gene associated with retinoid-IFN-induced mortality 19 (GRIM-19), as a novel IFN-beta/RA-inducible gene product, was identified as a potential tumor suppressor associated with growth inhibition and cell apoptosis. Recently, it has been reported that the apoptotic effects and apoptosis-related gene induction of GRIM-19 can be attenuated by GW112, indicating that GRIM-19 and GW112 are involved in a common signal transduction pathway. To investigate the signaling mechanisms that link GRIM-19 to GW112 and their functional role in tumor cell invasion and metastasis, we utilized adenovirus-mediated overexpression of GRIM-19 in the gastric cancer SGC-7901 cell line. We observed that enhanced expression of GRIM-19 not only downregulated GW112 but also decreased NF-small ka, CyrillicB binding activity. As a result, we found that tumor cell adhesion, migration, invasion and liver metastasis were inhibited. Additionally, upregulation of GRIM-19 also suppressed secretion of urokinase-type plasminogen activator (u-PA), matrix metalloproteinase (MMP)-2, 9 and vascular endothelial growth factor (VEGF). These results indicate that GRIM-19 acts as an upstream regulator of GW112 to block NF-small ka, CyrillicB binding activity, thereby inhibiting gastric cancer cell migration, invasion and metastasis. We conclude that adenoviral transfer of the GRIM-19 gene may be an efficacious approach to controlling the invasion and metastasis of human gastric cancer.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
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Regulação da Expressão Gênica
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Proteínas Reguladoras de Apoptose
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Neoplasias Hepáticas
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NADH NADPH Oxirredutases
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article