Urokinase induces stromal cell-derived factor-1 expression in human hepatocellular carcinoma cells

✍ Scribed by Wen-Hsiu Hsu; Cheng-Nan Chen; Hai-I Huang; Yi-Liang Lai; Chun-Yuh Teng; Wu-Hsien Kuo

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 439 KB
• Volume: 227
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.22777

✦ Synopsis

Abstract

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. J. Cell. Physiol. 227: 697–704, 2012. © 2011 Wiley Periodicals, Inc.