Home
Resources
Publications
A glycosphingolipid/caveolin-1 Signaling Complex Inhibits Motility of Human Ovarian Carcinoma Cells

A glycosphingolipid/caveolin-1 Signaling Complex Inhibits Motility of Human Ovarian Carcinoma Cells

Alessandro Prinetti, Ting Cao, Giuditta Illuzzi, Simona Prioni, Massimo Aureli, Nicoletta Gagliano, Giovanni Tredici, Virginia Rodriguez-Menendez, Vanna Chigorno, Sandro Sonnino

J Biol Chem. 2011 Nov 25;286(47):40900-10.

PMID: 21949119

Abstract:

The genetic (stable overexpression of sialyltransferase I, GM3 synthase) or pharmacological (selective pressure by N-(4-hydroxyphenyl)retinamide)) manipulation of A2780 human ovarian cancer cells allowed us to obtain clones characterized by higher GM3 synthase activity compared with wild-type cells. Clones with high GM3 synthase expression had elevated ganglioside levels, reduced in vitro cell motility, and enhanced expression of the membrane adaptor protein caveolin-1 with respect to wild-type cells. In high GM3 synthase-expressing clones, both depletion of gangliosides by treatment with the glucosylceramide synthase inhibitor D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol and silencing of caveolin-1 by siRNA were able to strongly increase in vitro cell motility. The motility of wild-type, low GM3 synthase-expressing cells was reduced in the presence of a Src inhibitor, and treatment of these cells with exogenous gangliosides, able to reduce their in vitro motility, inactivated c-Src kinase. Conversely, ganglioside depletion by D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol treatment or caveolin-1 silencing in high GM3 synthase-expressing cells led to c-Src kinase activation. In high GM3 synthase-expressing cells, caveolin-1 was associated with sphingolipids, integrin receptor subunits, p130(CAS), and c-Src forming a Triton X-100-insoluble noncaveolar signaling complex. These data suggest a role for gangliosides in regulating tumor cell motility by affecting the function of a signaling complex organized by caveolin-1, responsible for Src inactivation downstream to integrin receptors, and imply that GM3 synthase is a key target for the regulation of cell motility in human ovarian carcinoma.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP179248590-B	Src Kinase Inhibitor I - CAS 179248-59-0		179248-59-0	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: