Clustering of monosialyl-Gb5 initiates downstream signalling events leading to invasion of MCF-7 breast cancer cells.
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 alpha1 and beta1. Together these results suggest that the organization of crucial molecules in GEMs of MCF-7 cells is critical for their invasive properties.
Van Slambrouck
Severine
S
Laboratory of Biochemical and Biomedical Research, Department of Chemistry, New Mexico Tech, 801 Leroy Place, Socorro, NM 87801, USA.
Steelant
Wim F A
WF
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006028:Glycosphingolipids / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D021962:Membrane Microdomains / Q000737:chemistry* / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010713:Phosphatidylcholines / Q000494:pharmacology; D010742:Phospholipid Ethers; D015398:Signal Transduction
D006028:Glycosphingolipids; D016023:Integrins; D010713:Phosphatidylcholines; D010742:Phospholipid Ethers; C026659:edelfosine; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases; D020782:Matrix Metalloproteinases