Lithocholic acid upregulates uPAR and cell invasiveness via MAPK and AP-1 signaling in colon cancer cells

被引:45
作者
Baek, Min Kyung [1 ]
Park, Jung Sun [1 ]
Park, Ji Hye [1 ]
Kim, Mi Ha [1 ]
Kim, Ho Dong [1 ]
Bae, Woo Kyun [1 ]
Chung, Ik Joo [1 ]
Shin, Boo Ahn [1 ]
Do Jung, Young [1 ]
机构
[1] Chonnam Natl Univ, Sch Med, Dept Biochem, Ctr Biomed Human Resources,Brain Korea Project 21, Kwangju 501190, South Korea
关键词
LCA; Erk-1/2; AP-1; uPAR; Colon cancer; PLASMINOGEN-ACTIVATOR SYSTEM; UROKINASE RECEPTOR; PROTEIN-KINASE; GROWTH-FACTOR; BILE-ACIDS; INACTIVATION; PROLIFERATION; METASTASIS; INHIBITION; MIGRATION;
D O I
10.1016/j.canlet.2009.08.030
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The secondary bile acid lithocholic acid (LCA) induced expression of urokinase-type plasminogen activator receptor (uPAR) and enhanced cell invasiveness in colon cancer cells. A dominant negative mutant or a specific inhibitor of MEK-1 suppressed LCA-induced uPAR expression. Deletions and site-directed mutagenesis revealed that the AP-1 site was required for LCA-induced uPAR transcription. LCA-mediated enhanced cell invasiveness was partially abrogated by uPAR neutralizing antibody and inhibitors of both Erk-1/2 and AP-1. These results suggest that LCA induces uPAR expression via Erk-1/2 and AP-1 pathway and, in turn, stimulate invasiveness of human colon cancer cells. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:123 / 128
页数:6
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