PMID- 10521801
OWN - NLM
STAT- MEDLINE
DCOM- 19991119
LR  - 20190708
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 83
IP  - 5
DP  - 1999 Nov 26
TI  - HGF induces FAK activation and integrin-mediated adhesion in MTLn3 breast
      carcinoma cells.
PG  - 640-9
AB  - Expression of hepatocyte growth factor (HGF) and its tyrosine kinase receptor,
      c-Met, is positively correlated with breast carcinoma progression. We found that 
      in invasive and metastatic MTLn3 breast carcinoma cells, HGF stimulated both
      initial adhesion to and motility on the extracellular matrix (ECM) ligands
      laminin 1, type I collagen, and fibronectin. Next, analysis with
      function-perturbing antibodies showed that adhesion to the different ECM proteins
      was mediated through specific beta1 integrins. In MTLn3 cells, HGF induced rapid 
      tyrosine phosphorylation and activation of both c-Met and focal adhesion kinase
      (FAK). Cell anchorage and adhesion to the ECM substrates was required for
      HGF-induced FAK activation, since HGF failed to trigger tyrosine phosphorylation 
      of FAK in suspended cells. Our results provide evidence that the 2 signaling
      pathways, integrin/ECM and c-Met/HGF, cooperate synergistically to induce FAK
      activation in an adhesion-dependent manner, leading to enhanced cell adhesion and
      motility. Moreover, we found that a FRNK (the FAK-related non-kinase)-like
      molecule is expressed in MTLn3 cells. Since FRNK acts as a competitive inhibitor 
      of FAK function, our results suggest that a FRNK-like protein could facilitate
      disassembly of focal adhesions and likely be responsible for the HGF-induced
      scattering and motility of MTLn3 cells.
CI  - Copyright 1999 Wiley-Liss, Inc.
FAU - Beviglia, L
AU  - Beviglia L
AD  - Department of Stomatology, University of California, San Francisco, San
      Francisco, CA, USA.
FAU - Kramer, R H
AU  - Kramer RH
LA  - eng
GR  - DE 11436/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Antibodies)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (Integrins)
RN  - 0 (Laminin)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (laminin 1)
RN  - 42HK56048U (Tyrosine)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Focal Adhesion Kinase 1)
RN  - EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Ptk2 protein, rat)
SB  - IM
MH  - Animals
MH  - Antibodies/pharmacology
MH  - Cell Adhesion
MH  - Cell Adhesion Molecules/*drug effects/metabolism
MH  - Cell Movement
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Activation/drug effects
MH  - Epithelial Cells/drug effects
MH  - Extracellular Matrix Proteins
MH  - Female
MH  - Focal Adhesion Kinase 1
MH  - Focal Adhesion Protein-Tyrosine Kinases
MH  - Hepatocyte Growth Factor/*pharmacology
MH  - Integrins/antagonists & inhibitors/immunology/metabolism
MH  - Laminin
MH  - Mammary Neoplasms, Animal/*enzymology/metabolism/*pathology
MH  - Neoplasm Proteins/*drug effects/metabolism
MH  - Phosphorylation
MH  - Protein-Tyrosine Kinases/*drug effects/metabolism
MH  - Rats
MH  - Tumor Cells, Cultured/drug effects
MH  - Tyrosine/metabolism
EDAT- 1999/10/16 00:00
MHDA- 1999/10/16 00:01
CRDT- 1999/10/16 00:00
PHST- 1999/10/16 00:00 [pubmed]
PHST- 1999/10/16 00:01 [medline]
PHST- 1999/10/16 00:00 [entrez]
AID - 10.1002/(SICI)1097-0215(19991126)83:5<640::AID-IJC13>3.0.CO;2-D [pii]
AID - 10.1002/(sici)1097-0215(19991126)83:5<640::aid-ijc13>3.0.co;2-d [doi]
PST - ppublish
SO  - Int J Cancer. 1999 Nov 26;83(5):640-9. doi:
      10.1002/(sici)1097-0215(19991126)83:5<640::aid-ijc13>3.0.co;2-d.