Exp Mol Med.  2012 Jun;44(6):387-393.

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

Affiliations
  • 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. khchun@yuhs.ac
  • 5Brain Korea 21 Project for Medical Science of Yonsei University, Korea.

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
Full Text Links
  • EMM
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2021 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr