title: 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.
authors.affiliation: Department of Practical Pharmacy, College of Pharmacy, Kyung Hee University, Seoul, Korea.
authors.forename: Yuan-Guo
authors.initials: YG
authors.lastname: Wang
authors.forename: Seok-Jun
authors.initials: SJ
authors.lastname: Kim
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Baek
authors.forename: Hyun-Woo
authors.initials: HW
authors.lastname: Lee
authors.forename: Seo-Young
authors.initials: SY
authors.lastname: Jeong
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Chun
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000556:secondary*; D020781:Matrix Metalloproteinase 1 / Q000235:genetics* / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000378:metabolism* / Q000473:pathology* / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D009362:Neoplasm Metastasis; D011401:Promoter Regions, Genetic; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D018808:Transcription Factor AP-1 / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D000099169:Fos-Related Antigen 1
chemical_list: D037502:Galectin 3; D048031:JNK Mitogen-Activated Protein Kinases; D020781:Matrix Metalloproteinase 1; D016760:Proto-Oncogene Proteins c-fos; D034741:RNA, Small Interfering; D018808:Transcription Factor AP-1; D000099169:Fos-Related Antigen 1