Exp Mol Med.  2012 Jun;44(6):387-393.

Galectin-3 increases the motility of mouse melanoma cells by regulating matrix metalloproteinase-1 expression

• Wang YG
• Kim SJ
• Baek JH
• Lee HW
• Jeong SY
• Chun KH

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.

Keyword

galectin 3; matrix metalloproteinase 1; melanoma; neoplasm metastasis; RNA, small interfering; transcription factor AP-1

MeSH Terms

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