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KMID : 0620920120440060387
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Experimental & Molecular Medicine
2012 Volume.44 No. 6 p.387 ~ p.393
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Galectin-3 increases the motility of mouse melanoma cells by regulating matrix metalloproteinase-1 expression
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Wang Yuan-Guo
Kim Seok-Jun
Baek Jung-Hwan
Lee Hyun-Woo
Jeong Seo-Young
Chun Kyung-Hee
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Abstract
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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.
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KEYWORD
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galectin 3, matrix metalloproteinase 1, melanoma, neoplasm metastasis, RNA, small interfering, transcription factor AP-1
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