PMID- 16995838
OWN - NLM
STAT- MEDLINE
DCOM- 20070209
LR  - 20181113
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Print)
IS  - 0264-6021 (Linking)
VI  - 401
IP  - 3
DP  - 2007 Feb 1
TI  - Clustering of monosialyl-Gb5 initiates downstream signalling events leading to 
      invasion of MCF-7 breast cancer cells.
PG  - 689-99
AB  - 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.
FAU - Van Slambrouck, Severine
AU  - Van Slambrouck S
AD  - Laboratory of Biochemical and Biomedical Research, Department of Chemistry, New 
      Mexico Tech, 801 Leroy Place, Socorro, NM 87801, USA.
FAU - Steelant, Wim F A
AU  - Steelant WF
LA  - eng
GR  - P20 RR016480/RR/NCRR NIH HHS/United States
GR  - RR-16480/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Glycosphingolipids)
RN  - 0 (Integrins)
RN  - 0 (Phosphatidylcholines)
RN  - 0 (Phospholipid Ethers)
RN  - 1Y6SNA8L5S (edelfosine)
RN  - EC 2.7.10.2 (Focal Adhesion Kinase 1)
RN  - EC 2.7.10.2 (PTK2 protein, human)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Breast Neoplasms/*metabolism/*pathology
MH  - Cell Line, Tumor
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Female
MH  - Focal Adhesion Kinase 1/metabolism
MH  - Gene Expression Regulation, Neoplastic
MH  - Glycosphingolipids/chemistry/*metabolism
MH  - Humans
MH  - Integrins/metabolism
MH  - Matrix Metalloproteinases/metabolism
MH  - Membrane Microdomains/*chemistry/*metabolism
MH  - Neoplasm Invasiveness
MH  - Phosphatidylcholines/pharmacology
MH  - Phospholipid Ethers
MH  - *Signal Transduction
PMC - PMC1770852
EDAT- 2006/09/26 09:00
MHDA- 2007/02/10 09:00
PMCR- 2007/08/01
CRDT- 2006/09/26 09:00
PHST- 2006/09/26 09:00 [pubmed]
PHST- 2007/02/10 09:00 [medline]
PHST- 2006/09/26 09:00 [entrez]
PHST- 2007/08/01 00:00 [pmc-release]
AID - BJ20060944 [pii]
AID - bj4010689 [pii]
AID - 10.1042/BJ20060944 [doi]
PST - ppublish
SO  - Biochem J. 2007 Feb 1;401(3):689-99. doi: 10.1042/BJ20060944.