Biochem. J. (2007) 401
(689–699) (Printed in Great Britain)
Clustering of monosialyl-Gb5 initiates downstream signalling events leading to invasion of MCF-7 breast cancer cells
Severine VAN SLAMBROUCK and Wim F. A. STEELANT1
Laboratory of Biochemical and Biomedical Research, Department of Chemistry, New Mexico Tech, 801 Leroy Place, Socorro, NM 87801, U.S.A.
Invasion is a complex process controlled by secretion and activation of proteases, alteration of integrin levels and GSL (glycosphingolipid) patterns. Differential organization of GSLs with specific membrane proteins and signal transducers in GEMs (GSL-enriched microdomains), initiates signalling events to modify cellular phenotype. Although the GSL monosialyl-Gb5 has been linked with invasion, its functional role in invasion is poorly described and understood. To investigate this problem, we induced the invasion of human breast cancer cells and subsequently explored the underlying mechanism. In the present study, the invasion of human MCF-7 breast cancer cells is highly dependent on clustering of monosialyl-Gb5, and the subsequent activation of monosialyl-Gb5-associated focal adhesion kinase and cSrc in GEM leading to the downstream activation of extracellular-signal-regulated kinase (ERK). As a result, we observed increased expression levels and activity of matrix metalloproteinases-2 and -9, which correlated with decreased expression of integrins a1 and b1. Together these results suggest that the organization of crucial molecules in GEMs of MCF-7 cells is critical for their invasive properties.
Key words: extracellular-signal-regulated kinase (ERK), glycosphingolipid (GSL), glycosphingolipid-enriched microdomain (GEM), integrin, matrix metalloproteinase (MMP), monosialyl-Gb5 (MSGb5).
Abbreviations used: Ab, antibody; BCA, bicinchoninic acid; CMF-HBSS, calcium- and magnesium-free Hanks balanced salt solution; DMEM, Dulbecco's modified Eagle's medium; ECL, enhanced chemiluminescence; ERK, extracellular signal-regulated kinase; ET-18-OMe, 1-O-octadecyl-2-O-methyl-glycerophosphocholine; FAK, focal adhesion kinase; GD3, disialoganglioside 3; GEM, glycosphingolipid-enriched microdomain; GM3, monosialoganglioside 3; GSL, glycosphingolipid; HPTLC, high-performance TLC; mAb, monoclonal Ab; MAPK, mitogen-activated protein kinase; MEK, MAPK/ERK kinase; MMP, matrix metalloproteinase; MSGb5, monosialyl-globoside 5; MT, membrane type; PP1, 4-amino-1-tert-butyl-3-(1´-naphthyl)pyrazolo[3,4-d]pyrimidine; SSEA-4, stage-specific embryonic antigen-4.
1To whom correspondence should be addressed (email steelant@nmt.edu).
Received 22 June 2006/22 September 2006; accepted 25 September 2006
Published as BJ Immediate Publication 25 September 2006, doi:10.1042/BJ20060944
The Biochemical Society, London ©2007
Editorial Advisory Panel
RSS feeds
Table of contents by email
My BJ toolbox
