Urokinase induces stromal cell-derived factor-1 expression in human hepatocellular carcinoma cells.
J Cell Physiol
; 227(2): 697-704, 2012 Feb.
Article
en En
| MEDLINE
| ID: mdl-21465475
Both the urokinase-type plasminogen activator (uPA) and the uPA receptor (uPAR) play important roles with regard to hepatocellular carcinoma (HCC) progression and metastasis. Notably, the stromal cell-derived factor-1 (SDF-1) is an important chemokine involved in HCC pathology. However, the influence of uPA on SDF-1 expression in human HCC cells remains unknown. We investigated the mechanisms underlying the modulation of SDF-1 expression through uPA stimulation in human HCC SK-Hep-1 cells. SK-Hep-1 cells stimulation with uPA induced increases in the expression and secretion of SDF-1. By using specific inhibitors and small interfering RNA, we have demonstrated that the activation of extracellular signal-related kinase (ERK) and c-Jun-NH(2)-terminal kinase (JNK) pathways are critical for uPA-induced SDF-1 expression. Transcription factor ELISA and chromatin immunoprecipitation assays suggest that uPA increase Sp1- and AP-1-DNA-binding activities in SK-Hep-1 cells. Inhibition of Sp1 and AP-1 activations by specific siRNAs blocked the uPA-induced SDF-1 promoter activity and expression. The effect of uPA on SK-Hep-1 signaling and SDF-1 expression is mediated by uPAR. In summary, our findings serve to elucidate the uPA/uPAR downstream signaling, providing new insight into the function of uPA in HCC cells.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Activador de Plasminógeno de Tipo Uroquinasa
/
Regulación Neoplásica de la Expresión Génica
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Carcinoma Hepatocelular
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Quimiocina CXCL12
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Neoplasias Hepáticas
Límite:
Humans
Idioma:
En
Revista:
J Cell Physiol
Año:
2012
Tipo del documento:
Article
País de afiliación:
Taiwán
Pais de publicación:
Estados Unidos