EXPERIMENTAL and MOLECULAR MEDICINE, Vol. 44, No. 6, 387-393, June 2012 Galectin-3 increases the motility of mouse melanoma cells by regulating matrix metalloproteinase-1 expression Yuan-Guo Wang1, Seok-Jun Kim2,3,4, Jung-Hwan Baek4,5, Hyun-Woo Lee4, Seo-Young Jeong1 and Kyung-Hee Chun4,5,6 1Department of Practical Pharmacy College of Pharmacy Kyung Hee University Seoul 130-701, Korea 2Cancer Genomics Branch Division of Convergence Technology National Cancer Center Research Institute and Hospital Goyang 410-769, Korea 3Department of Biological Science Sungkyunkwan University Suwon 440-746, Korea 4Department of Biochemistry and Molecular Biology Yonsei University College of Medicine Seoul 120-752, Korea 5Brain Korea 21 Project for Medical Science of Yonsei University 6Corresponding author: Tel, 82-2-2228-1699; Fax, 82-2-312-5041; E-mail, khchun@yuhs.ac http://dx.doi.org/10.3858/emm.2012.44.6.044 Accepted 12 March 2012 Available Online 21 March 2012 Abbreviations: ChIP, chromatin immunoprecipitation; IP, immuno- precipitation; MMP-1, matrix metalloproteinase-1 Abstract Although mounting evidence indicates the involve- ment of galectin-3 in cancer progression and meta- stasis, the underlying molecular mechanisms remain largely unknown. In this study, we investigated the ef- fect and possible mechanism of galectin-3 on the mi- gration and invasion of B16F10, a metastatic melano- ma cell line, in which galectin-3 and matrix metal- loproteinase-1 (MMP-1) were both found to be highly expressed. Knockdown of galectin-3 with specific siRNA reduced migration and invasion, which was as- sociated 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 inter- acted with AP-1 and facilitated the binding of this com- plex to the MMP-1 promoter that drives MMP-1 transcription. Moreover, silencing of galectin-3 in- hibited 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, ga- lectin-3 facilitates cell migration and invasion in mela- noma 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. Keywords: galectin 3; matrix metalloproteinase 1; mel- anoma; neoplasm metastasis; RNA, small interfering; transcription factor AP-1 Introduction Galectin-3, a chimera-type of 31-kDa galactose- binding protein, is highly expressed in a variety of primary and metastatic tumors (Raz et al., 1990). Galectin-3 is associated with enhanced tumor progression, invasion and metastasis in various cancer cells, e.g., lung and gastric cancer cells (Hood and Cheresh, 2002; Liu and Rabinovich, 2005). Changes in circulating galectin-3 levels in cancer patients may reflect the metastatic spread of disseminating cancer cells (Yu, 2010). Thus, inhibition of galectin-3 may be a novel therapeutic approach for preventing metastasis and reducing cancer-associated mortality (Kim et al., 2010). However, the mechanisms underlying the role of galectin-3 in tumor progression and metastasis remain largely unclear. Matrix metalloproteinases (MMPs) facilitate tumor progression and metastasis (Khokha, 1994; Ahonen et al., 1998; Valente et al., 1998). Among these, MMP-1, MMP-2, MMP-9 and MT1-MMP are involved in human melanoma invasion (Walker and Woolley, 1999; Hofmann et al., 2005). MMP-1, which is capable of degrading type I, II and III collagens, is the only MMP subtype able to degrade triple helical collagens (Pardo and Selman, 2005). Recent Copyright ⓒ 2012 by the Korean Society for Biochemistry and Molecular Biology This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.