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

Exp Mol Med. 2012 Jun 30;44(6):387-93. doi: 10.3858/emm.2012.44.6.044.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites / genetics
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Galectin 3 / genetics
  • Galectin 3 / metabolism*
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Lung Neoplasms / secondary*
  • Matrix Metalloproteinase 1 / genetics*
  • Matrix Metalloproteinase 1 / metabolism*
  • Melanoma, Experimental / metabolism*
  • Melanoma, Experimental / pathology*
  • Melanoma, Experimental / 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*
  • Transcription Factor AP-1 / metabolism
  • Transcription, Genetic
  • Transcriptional Activation

Substances

  • Galectin 3
  • Proto-Oncogene Proteins c-fos
  • RNA, Small Interfering
  • Transcription Factor AP-1
  • fos-related antigen 1
  • JNK Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 1