PMID- 11535809
OWN - NLM
STAT- MEDLINE
DCOM- 20011101
LR  - 20181113
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 98
IP  - 19
DP  - 2001 Sep 11
TI  - Suppression of Ras-mediated tumorigenicity and metastasis through inhibition of 
      the Met receptor tyrosine kinase.
PG  - 10722-7
AB  - Mutations in the Ras family of GTP binding proteins represent one of the most 
      frequently observed genetic alterations in human cancers. We and others have 
      recently demonstrated that expression of Met, the tyrosine kinase receptor for 
      hepatocyte growth factor/scatter factor (HGF/SF), is significantly up-regulated 
      in Ras-transformed cells. Because HGF/SF-Met signaling is proposed to play a 
      prominent role in tumor development and progression, we assessed the possible 
      requirement for Met during Ras-mediated tumor growth and metastasis. To disrupt 
      endogenous Met signaling, we constructed dominant-negative mutants of both human 
      and murine Met and showed that these can inhibit HGF/SF-mediated Met signaling 
      and cell invasion of ras-transformed cells in vitro. Moreover, ectopic expression 
      of dominant-negative Met mutants reduced the s.c. tumor growth of ras-transformed 
      cells and dramatically suppressed their ability to form lung metastases in vivo. 
      Our data demonstrate that Met plays a prominent role during Ras-mediated tumor 
      growth and metastasis, and further suggest that agents that inhibit HGF/SF-Met 
      signaling may represent an important therapeutic avenue for the treatment of a 
      variety of malignant tumors.
FAU - Furge, K A
AU  - Furge KA
AD  - Molecular Oncology Laboratory, Van Andel Institute, 333 Bostwick, Northeast, 
      Grand Rapids, MI 49503, USA.
FAU - Kiewlich, D
AU  - Kiewlich D
FAU - Le, P
AU  - Le P
FAU - Vo, M N
AU  - Vo MN
FAU - Faure, M
AU  - Faure M
FAU - Howlett, A R
AU  - Howlett AR
FAU - Lipson, K E
AU  - Lipson KE
FAU - Vande Woude, G F
AU  - Vande Woude GF
FAU - Webb, C P
AU  - Webb CP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20010904
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 3.6.5.2 (Oncogene Protein p21(ras))
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Female
MH  - Hepatocyte Growth Factor/*metabolism
MH  - Humans
MH  - Lung Neoplasms/*secondary
MH  - Melanoma, Experimental/*secondary
MH  - Mice
MH  - Mice, Nude
MH  - Mutagenesis
MH  - Neoplasm Metastasis
MH  - Oncogene Protein p21(ras)/*metabolism
MH  - Proto-Oncogene Proteins c-met/genetics/*physiology
MH  - Tumor Cells, Cultured
PMC - PMC58533
EDAT- 2001/09/06 10:00
MHDA- 2001/11/03 10:01
PMCR- 2002/03/11
CRDT- 2001/09/06 10:00
PHST- 2001/09/06 10:00 [pubmed]
PHST- 2001/11/03 10:01 [medline]
PHST- 2001/09/06 10:00 [entrez]
PHST- 2002/03/11 00:00 [pmc-release]
AID - 191067898 [pii]
AID - 0678 [pii]
AID - 10.1073/pnas.191067898 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10722-7. doi: 
      10.1073/pnas.191067898. Epub 2001 Sep 4.