PMID- 11803465
OWN - NLM
STAT- MEDLINE
DCOM- 20020215
LR  - 20061115
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 21
IP  - 2
DP  - 2002 Jan 10
TI  - Requirement of Stat3 signaling for HGF/SF-Met mediated tumorigenesis.
PG  - 217-26
AB  - Hepatocyte Growth Factor/Scatter Factor (HGF/SF) mediates a wide variety of 
      cellular responses by acting through the Met tyrosine kinase receptor. 
      Inappropriate expression of HGF/SF and/or Met has been found in most types of 
      solid tumors and is often associated with poor prognosis. Importantly, 
      constitutional and sporadic activating mutations in Met have been discovered in 
      human papillary renal carcinomas and other cancers, while autocrine and paracrine 
      signaling of this receptor/ligand pair has been shown to contribute to 
      tumorigenesis and metastasis. Numerous downstream signaling molecules have been 
      implicated in HGF/SF-Met mediated tumorigenesis and metastasis. Stat3 is a 
      downstream signaling molecule activated by HGF/SF-Met signaling, and is reported 
      to contribute to cell transformation induced by a diverse set of oncoproteins. 
      Stat3 is constitutively activated in many primary tumors and tumor cell lines, 
      suggesting that signaling by this molecule may be important for cell 
      transformation. To address whether Stat3 is required for HGF/SF-Met mediated 
      tumorigenesis and metastasis, we introduced a dominant-negative form of Stat3, 
      Stat3beta into the human leiomyosarcoma cell line SK-LMS-1. We found that 
      Stat3beta has no effect on the transformed morphology, proliferation, invasion or 
      branching morphogenesis in vitro. By contrast, expression of Stat3beta affected 
      HGF/SF-Met mediated anchorage-independent colony formation and prevented 
      tumorigenic growth in athymic nu/nu mice. Thus, Met signaling through Stat3 
      provides an essential function for tumorigenic growth, which is manifested in 
      vitro by loss of anchorage-independent growth.
FAU - Zhang, Yu-Wen
AU  - Zhang YW
AD  - Laboratory of Molecular Oncology, Van Andel Research Institute, Grand Rapids, 
      Michigan, MI 49503, USA.
FAU - Wang, Ling-Mei
AU  - Wang LM
FAU - Jove, Richard
AU  - Jove R
FAU - Vande Woude, George F
AU  - Vande Woude GF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Acute-Phase Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Trans-Activators)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
SB  - IM
MH  - Acute-Phase Proteins/genetics/metabolism
MH  - Animals
MH  - Cell Division
MH  - Cell Line
MH  - Cell Transformation, Neoplastic/*drug effects
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Hepatocyte Growth Factor/*pharmacology
MH  - Morphogenesis/physiology
MH  - Recombinant Proteins/metabolism
MH  - STAT3 Transcription Factor
MH  - Signal Transduction
MH  - Trans-Activators/genetics/*metabolism
MH  - Transfection
EDAT- 2002/01/23 10:00
MHDA- 2002/02/16 10:01
CRDT- 2002/01/23 10:00
PHST- 2001/06/29 00:00 [received]
PHST- 2001/09/12 00:00 [revised]
PHST- 2001/10/01 00:00 [accepted]
PHST- 2002/01/23 10:00 [pubmed]
PHST- 2002/02/16 10:01 [medline]
PHST- 2002/01/23 10:00 [entrez]
AID - 10.1038/sj.onc.1205004 [doi]
PST - ppublish
SO  - Oncogene. 2002 Jan 10;21(2):217-26. doi: 10.1038/sj.onc.1205004.