title: Silencing of GM3 synthase suppresses lung metastasis of murine breast cancer cells.
abstract: BACKGROUND
  Gangliosides are sialic acid containing glycosphingolipids that are ubiquitously distributed on vertebrate plasma membranes. GM3, a precursor for most of the more complex ganglioside species, is synthesized by GM3 synthase. Although total ganglioside levels are significantly higher in breast tumor tissue than in normal mammary tissue, the roles played by gangliosides in breast cancer formation and metastasis are not clear.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Molecular Biology, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, China.
authors.forename: Yuchao
authors.initials: Y
authors.lastname: Gu
authors.forename: Junhua
authors.initials: J
authors.lastname: Zhang
authors.forename: Wenyi
authors.initials: W
authors.lastname: Mi
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.forename: Feng
authors.initials: F
authors.lastname: Han
authors.forename: Xinzhi
authors.initials: X
authors.lastname: Lu
authors.forename: Wengong
authors.initials: W
authors.lastname: Yu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000556:secondary; D051379:Mice; D012799:Sialyltransferases / Q000096:biosynthesis*
chemical_list: D012799:Sialyltransferases; C021343:haematoside synthetase