PMID- 15838885
OWN - NLM
STAT- MEDLINE
DCOM- 20050919
LR  - 20091119
IS  - 0730-2312 (Print)
IS  - 0730-2312 (Linking)
VI  - 95
IP  - 4
DP  - 2005 Jul 1
TI  - Activation of the c-Met receptor complex in fibroblasts drives invasive cell 
      behavior by signaling through transcription factor STAT3.
PG  - 805-16
AB  - c-Met is the receptor for hepatocyte growth factor/scatter factor (HGF/SF). It 
      mediates multiple cellular responses in development and adult life, and c-Met 
      hyperactivity is associated with malignant transformation of cells and the 
      acquisition of metastatic properties. Signal transducer and activator of 
      transcription 3 (STAT3) has been shown to contribute to c-Met-mediated cell 
      motility and is, thus, potentially involved in the control of invasive cell 
      behavior. We have functionally reconstituted c-Met-dependent signal transduction 
      in fibroblasts with the aim of studying Met-driven cell invasiveness and the role 
      of STAT3 in this phenomenon. Activation of the system was achieved by means of a 
      hybrid receptor comprising the extracellular domain of the nerve growth factor 
      (NGF) receptor TrkA, the cytoplasmic part of c-Met and a C-terminally fused blue 
      fluorescent protein (BFP). In addition, a GFP-tagged derivative of adaptor 
      protein Gab1 was expressed. NGF-stimulation of mouse fibroblasts expressing 
      tagged versions of both Trk-Met and Gab1 with NGF resulted in 
      anchorage-independent growth and enhanced invasiveness. By freeze-fracture 
      cytochemistry and electron microscopy, we were able to visualize the 
      ligand-induced formation of multivalent receptor complex assemblies within the 
      cell membrane. NGF-stimulation of the heterologous receptor system evoked 
      activation of STAT3 as evidenced by tyrosine phosphorylation and the formation of 
      STAT3 clusters at the cell membrane. siRNA-mediated ablation of STAT3 expression 
      resulted in a drastic reduction of c-Met-driven invasiveness, indicating an 
      important role of STAT3 in the control of this particularly relevant property of 
      transformed cells.
FAU - Cramer, Alexander
AU  - Cramer A
AD  - Institute of Biochemistry I, Friedrich Schiller University Jena, Nonnenplan 2, 
      07743 Jena, Germany.
FAU - Kleiner, Sandra
AU  - Kleiner S
FAU - Westermann, Martin
AU  - Westermann M
FAU - Meissner, Anja
AU  - Meissner A
FAU - Lange, Anika
AU  - Lange A
FAU - Friedrich, Karlheinz
AU  - Friedrich K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, mouse)
RN  - 0 (Trans-Activators)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Animals
MH  - Cell Membrane/metabolism
MH  - *Cell Movement
MH  - Contact Inhibition
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Fibroblasts
MH  - Mice
MH  - Multigene Family
MH  - NIH 3T3 Cells
MH  - Proto-Oncogene Proteins c-met/*chemistry/genetics/*metabolism
MH  - RNA, Small Interfering/genetics/metabolism
MH  - STAT3 Transcription Factor
MH  - *Signal Transduction
MH  - Trans-Activators/genetics/*metabolism
EDAT- 2005/04/20 09:00
MHDA- 2005/09/20 09:00
CRDT- 2005/04/20 09:00
PHST- 2005/04/20 09:00 [pubmed]
PHST- 2005/09/20 09:00 [medline]
PHST- 2005/04/20 09:00 [entrez]
AID - 10.1002/jcb.20459 [doi]
PST - ppublish
SO  - J Cell Biochem. 2005 Jul 1;95(4):805-16. doi: 10.1002/jcb.20459.