Lithocholic acid upregulates uPAR and cell invasiveness via MAPK and AP-1 signaling in colon cancer cells.
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.
Center for Biomedical Human Resources at Chonnam National University, Chonnam National University Medical School, Gwangju, Republic of Korea.
Min Kyung
MK
Baek
Jung Sun
JS
Park
Ji Hye
JH
Park
Mi Ha
MH
Kim
Ho Dong
HD
Kim
Woo Kyun
WK
Bae
Ik Joo
IJ
Chung
Boo Ahn
BA
Shin
Young Do
YD
Jung
D015152:Blotting, Northern; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D024202:Electrophoretic Mobility Shift Assay; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008095:Lithocholic Acid / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation
D012333:RNA, Messenger; D055293:Receptors, Urokinase Plasminogen Activator; D018808:Transcription Factor AP-1; D008095:Lithocholic Acid; D020928:Mitogen-Activated Protein Kinases