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Silencing of GM3 synthase suppresses lung metastasis of murine breast cancer cellsDOI: 10.1186/bcr1841 Abstract: To investigate the roles of gangliosides in breast tumor development, GM3 synthase was silenced in the highly metastatic 4T1 cells and over-expressed in the non-metastatic 67NR cells. The behavior of breast cancer cells was examined in vitro using migration assay, invasion assay, and soft agar assay. Tumor formation and metastasis in vivo were examined using a well established mouse mammary tumor model.GM3 synthase silencing in 4T1 cells significantly inhibited cell migration, invasion and anchorage-independent growth in vitro, and lung metastasis in vivo. In addition, over-expression of GM3 synthase in nonmetastatic 67NR cells significantly induced cell migration and anchorage-independent growth. Further studies indicated that activation of the phosphoinositide-3 kinase/Akt pathway, and consequently inhibition of nuclear factor of activated T cell (NFAT)1 expression, could be the mechanism underlying the suppression of breast cancer migration/invasion induced by GM3 synthase silencing.Our findings indicate that GM3 synthase silencing suppressed lung metastasis in murine breast cancer cells. The molecular mechanism that underlies GM3 synthase mediated migration and invasion was inhibition of the phosphoinositide-3 kinase/Akt pathway. The findings suggest that GM3 synthase may be of value as a therapeutic target in breast cancer.Gangliosides are sialic acid containing glycosphingolipids that are ubiquitously distributed on vertebrate plasma membranes [1]. They participate in the regulation of various cellular functions, including cell proliferation, apoptosis, migration, and invasion [2-4]. Numerous studies have demonstrated that abnormal ganglioside expression is strongly associated with the malignancy of cancer cells [5]. The ganglioside content is upregulated in some metastasizing tumor cells, such as lymphoma cells, fibrosarcoma cells, and melanoma cells [6-8]. However, there is an inverse relation between metastasis properties and ganglioside content in some typ
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