GM3 synthase overexpression results in reduced cell motility and in caveolin-1 upregulation in human ovarian carcinoma cells.
In this paper, we describe the effects of the expression of GM3 synthase at high levels in human ovarian carcinoma cells. Overexpression of GM3 synthase in A2780 cells consistently resulted in elevated ganglioside (GM3, GM2 and GD1a) levels. GM3 synthase overexpressing cells had a growth rate similar to wild-type cells, but showed a strongly reduced in vitro cell motility accompanied by reduced levels of the epithelial-mesenchymal transition marker alpha smooth muscle actin. A similar reduction in cell motility was observed upon treatment with exogenous GM3, GM2, and GM1, but not with GD1a. A photolabeling experiment using radioactive and photoactivable GM3 highlighted several proteins directly interacting with GM3. Among those, caveolin-1 was identified as a GM3-interacting protein in GM3 synthase overexpressing cells. Remarkably, caveolin-1 was markedly upregulated in GM3 synthase overexpressing cells. In addition, the motility of low GM3 synthase expressing cells was also reduced in the presence of a Src kinase inhibitor; on the other hand, higher levels of the inactive form of c-Src were detected in GM3 synthase overexpressing cells, associated with a ganglioside- and caveolin-rich detergent insoluble fraction.
Prinetti
Alessandro
A
Department of Medical Chemistry, Biochemistry and Biotechnology, Center of Excellence on Neurodegenerative Diseases, Biochemistry and Biotechnology, University of Milan, Italy. alessandro.prinetti@unimi.it
Aureli
Massimo
M
Illuzzi
Giuditta
G
Prioni
Simona
S
Nocco
Valentina
V
Scandroglio
Federica
F
Gagliano
Nicoletta
N
Tredici
Giovanni
G
Rodriguez-Menendez
Virginia
V
Chigorno
Vanna
V
Sonnino
Sandro
S
D000199:Actins / Q000378:metabolism; D002277:Carcinoma / Q000201:enzymology*; D051242:Caveolin 1 / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D002465:Cell Movement; D017931:DNA Primers / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010051:Ovarian Neoplasms / Q000201:enzymology*; D012799:Sialyltransferases / Q000096:biosynthesis*; D013107:Sphingolipids / Q000737:chemistry; D019061:src-Family Kinases / Q000378:metabolism
D000199:Actins; D051242:Caveolin 1; D017931:DNA Primers; D004791:Enzyme Inhibitors; D013107:Sphingolipids; D012799:Sialyltransferases; C021343:haematoside synthetase; D019061:src-Family Kinases