PMID- 10047444
OWN - NLM
STAT- MEDLINE
DCOM- 19990317
LR  - 20131121
IS  - 0014-4827 (Print)
IS  - 0014-4827 (Linking)
VI  - 247
IP  - 1
DP  - 1999 Feb 25
TI  - Involvement of focal adhesion kinase in inhibition of motility of human breast
      cancer cells by sphingosine 1-phosphate.
PG  - 17-28
AB  - Sphingosine 1-phosphate (SPP), a bioactive sphingolipid metabolite, inhibits
      chemoinvasiveness of the aggressive, estrogen-independent MDA-MB-231 human breast
      cancer cell line. As in many other cell types, SPP stimulated proliferation of
      MDA-MB-231 cells, albeit to a lesser extent. Treatment of MDA-MB-231 cells with
      SPP had no significant effect on their adhesiveness to Matrigel, and only high
      concentrations of SPP partially inhibited matrix metalloproteinase-2 activation
      induced by Con A. However, SPP at a concentration that strongly inhibited
      invasiveness also markedly reduced chemotactic motility. To investigate the
      molecular mechanisms by which SPP interferes with cell motility, we examined
      tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin, which are
      important for organization of focal adhesions and cell motility. SPP rapidly
      increased tyrosine phosphorylation of FAK and paxillin and of the
      paxillin-associated protein Crk. Overexpression of FAK and kinase-defective FAK
      in MDA-MB-231 cells resulted in a slight increase in motility without affecting
      the inhibitory effect of SPP, whereas expression of FAK with a mutation of the
      major autophosphorylation site (F397) abolished the inhibitory effect of SPP on
      cell motility. In contrast, the phosphoinositide 3'-kinase inhibitor, wortmannin,
      inhibited chemotactic motility in both vector and FAK-F397-transfected cells. Our
      results suggest that autophosphorylation of FAK on Y397 may play an important
      role in SPP signaling leading to decreased cell motility.
CI  - Copyright 1999 Academic Press.
FAU - Wang, F
AU  - Wang F
AD  - Department of Biochemistry and Molecular Biology, Georgetown University Medical
      Center, 3900 Reservoir Road, NW, Washington, DC, 20007, USA.
FAU - Nohara, K
AU  - Nohara K
FAU - Olivera, A
AU  - Olivera A
FAU - Thompson, E W
AU  - Thompson EW
FAU - Spiegel, S
AU  - Spiegel S
LA  - eng
GR  - 1RO1 CA61774/CA/NCI 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  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Drug Combinations)
RN  - 0 (Laminin)
RN  - 0 (Lysophospholipids)
RN  - 0 (PXN protein, human)
RN  - 0 (Paxillin)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proteoglycans)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-crk)
RN  - 119978-18-6 (matrigel)
RN  - 26993-30-6 (sphingosine 1-phosphate)
RN  - 42HK56048U (Tyrosine)
RN  - 9007-34-5 (Collagen)
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, human)
RN  - EC 3.4.24.- (Gelatinases)
RN  - EC 3.4.24.- (Metalloendopeptidases)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - NGZ37HRE42 (Sphingosine)
SB  - IM
MH  - Breast Neoplasms/*enzymology/*pathology
MH  - Cell Adhesion/drug effects
MH  - Cell Adhesion Molecules/*physiology
MH  - Cell Division/drug effects
MH  - *Cell Movement/drug effects
MH  - Chemotaxis/drug effects
MH  - Collagen/metabolism
MH  - Cytoskeletal Proteins/metabolism
MH  - Drug Combinations
MH  - Enzyme Activation/drug effects
MH  - Focal Adhesion Kinase 1
MH  - Focal Adhesion Protein-Tyrosine Kinases
MH  - Gelatinases/antagonists & inhibitors
MH  - Humans
MH  - Laminin/metabolism
MH  - *Lysophospholipids
MH  - Matrix Metalloproteinase 2
MH  - Metalloendopeptidases/antagonists & inhibitors
MH  - Paxillin
MH  - Phosphoproteins/metabolism
MH  - Phosphorylation
MH  - Protein-Tyrosine Kinases/*physiology
MH  - Proteoglycans/metabolism
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-crk
MH  - Sphingosine/*analogs & derivatives/physiology
MH  - Tumor Cells, Cultured
MH  - Tyrosine/metabolism
EDAT- 1999/02/27 03:13
MHDA- 2000/02/19 09:00
CRDT- 1999/02/27 03:13
PHST- 1999/02/27 03:13 [pubmed]
PHST- 2000/02/19 09:00 [medline]
PHST- 1999/02/27 03:13 [entrez]
AID - S0014-4827(98)94327-0 [pii]
AID - 10.1006/excr.1998.4327 [doi]
PST - ppublish
SO  - Exp Cell Res. 1999 Feb 25;247(1):17-28. doi: 10.1006/excr.1998.4327.