PMID- 15389640
OWN - NLM
STAT- MEDLINE
DCOM- 20050407
LR  - 20121115
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 202
IP  - 3
DP  - 2005 Mar
TI  - Effect of tumor-associated mutant E-cadherin variants with defects in exons 8 or 
      9 on matrix metalloproteinase 3.
PG  - 805-13
AB  - Tumor progression is characterized by loss of cell adhesion and increase of 
      invasion and metastasis. The cell adhesion molecule E-cadherin is frequently 
      down-regulated or mutated in tumors. In addition to down-regulation of cell 
      adhesion, degradation of the extracellular matrix by matrix metalloproteinases is 
      necessary for tumor cell spread. To investigate a possible link between 
      E-cadherin and matrix metalloproteinase 3 (MMP-3), we examined expression of 
      MMP-3 in human MDA-MB-435S cells transfected with wild-type (wt) or three 
      different tumor-associated mutant E-cadherin variants with alterations in exons 8 
      or 9, originally identified in gastric carcinoma patients. In the presence of wt 
      E-cadherin, the MMP-3 protein level was decreased in cellular lysates and in the 
      supernatant where a secreted form of the protein is detectable. Down-regulation 
      of MMP-3 was not found in MDA-MB-435S transfectants expressing mutant E-cadherin 
      variants which indicates that E-cadherin mutations interfere with the MMP-3 
      suppressing function of E-cadherin. The mechanism of regulation of MMP-3 by 
      E-cadherin is presently not clear. We have previously found that cell motility is 
      enhanced by expression of the mutant E-cadherin variants used in this study. 
      Here, we found that application of the synthetic inhibitor of MMP-3 NNGH and 
      small interfering RNA (siRNA) directed against MMP-3 reduce mutant 
      E-cadherin-enhanced cell motility. Taken together, our results point to a 
      functional link between MMP-3 and E-cadherin. MMP-3 is differentially regulated 
      by expression of wt or mutant E-cadherin. On the other hand, MMP-3 plays a role 
      in the enhancement of cell motility by mutant E-cadherin. Both observations may 
      be highly relevant for tumor progression since they concern degradation of the 
      extracellular matrix and tumor cell spread.
CI  - 2004 Wiley-Liss, Inc.
FAU - Fuchs, Margit
AU  - Fuchs M
AD  - Technische Universitat Munchen, Klinikum rechts der Isar, Institut fur Allgemeine 
      Pathologie und Pathologische Anatomie, Munchen, Germany.
FAU - Hermannstadter, Christine
AU  - Hermannstadter C
FAU - Specht, Katja
AU  - Specht K
FAU - Knyazev, Pjotr
AU  - Knyazev P
FAU - Ullrich, Axel
AU  - Ullrich A
FAU - Rosivatz, Erika
AU  - Rosivatz E
FAU - Busch, Raymonde
AU  - Busch R
FAU - Hutzler, Peter
AU  - Hutzler P
FAU - Hofler, Heinz
AU  - Hofler H
FAU - Luber, Birgit
AU  - Luber B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Cadherins)
RN  - 0 (Matrix Metalloproteinase Inhibitors)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Biological Assay
MH  - Cadherins/*genetics/*metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Cell Shape
MH  - *Exons
MH  - Gene Expression Profiling
MH  - Humans
MH  - Matrix Metalloproteinase 3/genetics/*metabolism
MH  - Matrix Metalloproteinase Inhibitors
MH  - *Mutation
MH  - Neoplasms/genetics/*metabolism/*pathology
MH  - Oligonucleotide Array Sequence Analysis
EDAT- 2004/09/25 05:00
MHDA- 2005/04/09 09:00
CRDT- 2004/09/25 05:00
PHST- 2004/09/25 05:00 [pubmed]
PHST- 2005/04/09 09:00 [medline]
PHST- 2004/09/25 05:00 [entrez]
AID - 10.1002/jcp.20192 [doi]
PST - ppublish
SO  - J Cell Physiol. 2005 Mar;202(3):805-13. doi: 10.1002/jcp.20192.