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首页> 外文期刊>Journal of Cellular Physiology >Urokinase induces stromal cell-derived factor-1 expression in human hepatocellular carcinoma cells.
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Urokinase induces stromal cell-derived factor-1 expression in human hepatocellular carcinoma cells.

机译：尿激酶诱导基质细胞衍生因子- 1表达在人类肝细胞癌细胞。

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摘要

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.
机译：无论是urokinase-type纤溶酶原激活物(uPA)和uPA受体(uPAR)扮演了一个重要的角色对于肝细胞癌(HCC)进展和转移。基质细胞衍生因子- 1 (SDF-1)是一个重要的趋化因子参与肝癌病理。然而,uPA SDF-1上表达的影响在人类肝癌细胞仍然是未知的。调查的机制通过uPA调制SDF-1表达在人类肝细胞癌SK-Hep-1刺激细胞。细胞与uPA诱导增加刺激SDF-1的表达和分泌。特定的抑制剂和小干扰RNA,我们表明,激活了吗细胞外signal-related激酶(ERK)和c-Jun-NH(2)终端激酶(物)的途径的关键uPA-induced SDF-1表达式。转录因子ELISA和染色质免疫沉淀反应化验表明,uPA增加Sp1和AP-1-DNA-binding活动SK-Hep-1细胞。激活特定siRNAs封锁了uPA-induced SDF-1和推广活动表达式。信号和SDF-1表达式是由uPAR。uPA / uPAR下游信号,提供新的洞察uPA在肝癌细胞的功能。

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