Galectin-3 increases the motility of mouse melanoma cells by regulating matrix metalloproteinase-1 expression.
- Author:
Yuan Guo WANG
1
;
Seok Jun KIM
;
Jung Hwan BAEK
;
Hyun Woo LEE
;
Seo Young JEONG
;
Kyung Hee CHUN
Author Information
1. Department of Practical Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 130-701, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
galectin 3;
matrix metalloproteinase 1;
melanoma;
neoplasm metastasis;
RNA, small interfering;
transcription factor AP-1
- MeSH:
Animals;
Binding Sites/genetics;
Cell Line, Tumor;
Cell Movement;
Cell Proliferation;
Galectin 3/genetics/*metabolism;
JNK Mitogen-Activated Protein Kinases/metabolism;
Lung Neoplasms/drug therapy/genetics/*secondary;
Matrix Metalloproteinase 1/*genetics/*metabolism;
Melanoma, Experimental/*metabolism/*pathology/secondary;
Mice;
Mice, Inbred C57BL;
NIH 3T3 Cells;
Neoplasm Metastasis;
Promoter Regions, Genetic;
Proto-Oncogene Proteins c-fos/metabolism;
RNA Interference;
RNA, Small Interfering;
Transcription Factor AP-1/*genetics/metabolism;
Transcription, Genetic;
Transcriptional Activation
- From:Experimental & Molecular Medicine
2012;44(6):387-393
- CountryRepublic of Korea
- Language:English
-
Abstract:
Although mounting evidence indicates the involvement of galectin-3 in cancer progression and metastasis, the underlying molecular mechanisms remain largely unknown. In this study, we investigated the effect and possible mechanism of galectin-3 on the migration and invasion of B16F10, a metastatic melanoma cell line, in which galectin-3 and matrix metalloproteinase-1 (MMP-1) were both found to be highly expressed. Knockdown of galectin-3 with specific siRNA reduced migration and invasion, which was associated with reduced expression of MMP-1. To further investigate the underlying mechanism, we examined the effect of galectin-3 knockdown on the activity of AP-1, a transcriptional factor regulating MMP-1 expression. We found that galectin-3 directly interacted with AP-1 and facilitated the binding of this complex to the MMP-1 promoter that drives MMP-1 transcription. Moreover, silencing of galectin-3 inhibited binding of fra-1 and c-Jun to promoter sites of MMP-1 gene. Consistent with these in vitro findings, our in vivo study demonstrated that galectin-3 shRNA treatment significantly reduced the total number of mouse lung metastatic nodules. Taken together, galectin-3 facilitates cell migration and invasion in melanoma in vitro and can induce metastasis in vivo, in part through, regulating the transcription activity of AP-1 and thereby up-regulating MMP-1 expression.
