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Glycobiology Advance Access originally published online on September 16, 2009
Glycobiology 2010 20(1):62-77; doi:10.1093/glycob/cwp143
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© The Author 2009. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

GM3 synthase overexpression results in reduced cell motility and in caveolin-1 upregulation in human ovarian carcinoma cells

Alessandro Prinetti1,3, Massimo Aureli2,3, Giuditta Illuzzi2,3, Simona Prioni2,3, Valentina Nocco3, Federica Scandroglio3, Nicoletta Gagliano4, Giovanni Tredici5, Virginia Rodriguez-Menendez5, Vanna Chigorno3 and Sandro Sonnino3

3 Department of Medical Chemistry, Biochemistry and Biotechnology, Center of Excellence on Neurodegenerative Diseases, Biochemistry and Biotechnology
4 Department of Human Morphology, University of Milan, 20090 Segrate
5 Department of Neuroscience and Biomedical Technologies, University of Milan-Bicocca, 20052 Monza, Italy

1 To whom correspondence should be addressed: Tel: +39-02-50330376; Fax: +39-02-50330365; e-mail: alessandro.prinetti{at}unimi.it

Received on May 29, 2009; revised on September 9, 2009; accepted on September 9, 2009

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.

Key words: caveolin-1 / gangliosides / GM3 synthase / motility / ovarian cancer

2 These Authors equally contributed to the paper.


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