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

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.

DOI: 10.3858/emm.2012.44.6.044

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@inproceedings{Wang2012Galectin3IT, title={Galectin-3 increases the motility of mouse melanoma cells by regulating matrix metalloproteinase-1 expression}, author={Yuan-Guo Wang and Seok-Jun Kim and Jung-Hwan Baek and Hyun-Woo Lee and Seo-Young Jeong and K Chun}, booktitle={Experimental & Molecular Medicine}, year={2012} }