PMID- 17552361
OWN - NLM
STAT- MEDLINE
DCOM- 20070710
LR  - 20161124
IS  - 1359-4117 (Print)
IS  - 1359-4117 (Linking)
VI  - 6
IP  - 3
DP  - 2007
TI  - Activation of Src by c-Met overexpression mediates metastatic properties of 
      colorectal carcinoma cells.
PG  - 205-17
AB  - Overexpression and/or activation of c-Met, the protein tyrosine kinase receptor 
      for the hepatocyte growth factor/scatter factor (HGF/SF), and the protein 
      tyrosine kinase, Src, have been implicated in the progression and metastasis of 
      human colorectal carcinoma (CRC). Previously, through ribozyme-mediated c-Met 
      downregulation, we demonstrated a causal role for c-Met in CRC tumorigenesis and 
      the production of liver metastases from the highly metastatic CRC cell line, 
      KM20. Analysis of signaling intermediates downstream of c-Met demonstrated a 
      specific reduction of Src activity with minimal effect on Erk1/2 and Akt 
      following c-Met downregulation. As Src has been shown to upregulate Vascular 
      Endothelial Growth Factor (VEGF), we sought to determine if the reduced tumor 
      size and incidence could be due to reduced vessel formation in the c-Met 
      downregulated clones. Here we show that tumors produced from c-Met downregulated 
      cells have significantly reduced vessel density in tumors, correlating with a 
      reduction in VEGF production. Additionally, the Src selective inhibitor, PP2, 
      significantly reduced basal VEGF production in KM20 parental cells, and this 
      effect could be rescued by HGF treatment. PP2 reduced basal proliferation, 
      migration, and anchorage-independent growth. Furthermore, PP2 treatment 
      demonstrated a dose-dependent decrease in HGF induced migration. In contrast, PP2 
      treatment only had a minor effect on HGF induced anchorage-independent growth. 
      Collectively, these data demonstrate a significant role for c-Met-mediated Src 
      activation in processes involved in CRC tumorigenesis and liver metastasis.
FAU - Herynk, Matthew H
AU  - Herynk MH
AD  - Department of Cancer Biology, University of Texas M. D. Anderson Cancer Center, 
      The Program in Cancer Biology, University of Texas-Houston Health Science Center, 
      Graduate School of Biomedical Sciences, Houston, TX 77030, USA.
FAU - Zhang, Jing
AU  - Zhang J
FAU - Parikh, Nila U
AU  - Parikh NU
FAU - Gallick, Gary E
AU  - Gallick GE
LA  - eng
GR  - CA65527/CA/NCI NIH HHS/United States
GR  - T32 CA60440-9/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Exp Ther Oncol
JT  - Journal of experimental therapeutics & oncology
JID - 9604933
RN  - 0 (Proliferating Cell Nuclear Antigen)
RN  - 0 (Tetrazolium Salts)
RN  - 0 (Thiazoles)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EUY85H477I (thiazolyl blue)
SB  - IM
MH  - Autoradiography
MH  - Blotting, Northern
MH  - Blotting, Western
MH  - Cell Line, Tumor
MH  - Cell Movement/physiology
MH  - Colorectal Neoplasms/*genetics/*pathology
MH  - Down-Regulation/physiology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Extracellular Signal-Regulated MAP Kinases/physiology
MH  - Gene Expression Regulation, Neoplastic/*genetics/*physiology
MH  - Genes, src/*physiology
MH  - Humans
MH  - Immunohistochemistry
MH  - Immunoprecipitation
MH  - Neoplasm Metastasis/*genetics/*pathology
MH  - Neovascularization, Pathologic/genetics/pathology
MH  - Phosphorylation
MH  - Prognosis
MH  - Proliferating Cell Nuclear Antigen/genetics/metabolism
MH  - Proto-Oncogene Proteins c-akt/genetics
MH  - Proto-Oncogene Proteins c-met/*biosynthesis/genetics
MH  - Signal Transduction/genetics/physiology
MH  - Tetrazolium Salts
MH  - Thiazoles
MH  - Tumor Stem Cell Assay
MH  - Vascular Endothelial Growth Factor A/biosynthesis/genetics
EDAT- 2007/06/08 09:00
MHDA- 2007/07/11 09:00
CRDT- 2007/06/08 09:00
PHST- 2007/06/08 09:00 [pubmed]
PHST- 2007/07/11 09:00 [medline]
PHST- 2007/06/08 09:00 [entrez]
PST - ppublish
SO  - J Exp Ther Oncol. 2007;6(3):205-17.