Activation of the c-Met receptor complex in fibroblasts drives invasive cell behavior by signaling through transcription factor STAT3
(2005) In Journal of Cellular Biochemistry 95(4). p.805-816- Abstract
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... (More)
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.
(Less)
- author
- Cramer, Alexander ; Kleiner, Sandra ; Westermann, Martin ; Meissner, Anja LU ; Lange, Anika and Friedrich, Karlheinz
- publishing date
- 2005-07-01
- type
- Contribution to journal
- publication status
- published
- keywords
- c-Met, Invasiveness, Receptor activation, STAT3
- in
- Journal of Cellular Biochemistry
- volume
- 95
- issue
- 4
- pages
- 12 pages
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:15838885
- scopus:24744451993
- ISSN
- 0730-2312
- DOI
- 10.1002/jcb.20459
- language
- English
- LU publication?
- no
- id
- 6276f079-2a08-411d-944e-f2335abc2ee2
- date added to LUP
- 2017-05-23 22:26:51
- date last changed
- 2024-06-09 17:14:34
@article{6276f079-2a08-411d-944e-f2335abc2ee2, abstract = {{<p>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.</p>}}, author = {{Cramer, Alexander and Kleiner, Sandra and Westermann, Martin and Meissner, Anja and Lange, Anika and Friedrich, Karlheinz}}, issn = {{0730-2312}}, keywords = {{c-Met; Invasiveness; Receptor activation; STAT3}}, language = {{eng}}, month = {{07}}, number = {{4}}, pages = {{805--816}}, publisher = {{Wiley-Blackwell}}, series = {{Journal of Cellular Biochemistry}}, title = {{Activation of the c-Met receptor complex in fibroblasts drives invasive cell behavior by signaling through transcription factor STAT3}}, url = {{http://dx.doi.org/10.1002/jcb.20459}}, doi = {{10.1002/jcb.20459}}, volume = {{95}}, year = {{2005}}, }