PMID- 11865026
OWN - NLM
STAT- MEDLINE
DCOM- 20020702
LR  - 20220215
IS  - 0021-9533 (Print)
IS  - 0021-9533 (Linking)
VI  - 115
IP  - Pt 4
DP  - 2002 Feb 15
TI  - N-WASP activation by a beta1-integrin-dependent mechanism supports 
      PI3K-independent chemotaxis stimulated by urokinase-type plasminogen activator.
PG  - 699-711
AB  - Urokinase-type plasminogen activator (uPA)-uPA receptor (uPAR) and epidermal 
      growth factor (EGF)-EGF receptor (EGFR) expression is highly correlated with 
      breast cancer metastasis. Phosphoinositide 3-kinase (PI3K), small Rho GTPases, 
      such as Cdc42 and Rac1, and neuronal Wiskott Aldrich syndrome protein (N-WASP) 
      are key effectors that regulate dynamic changes in the actin cytoskeleton and 
      cell migration. uPA- and EGF-stimulated chemotaxis, cytoskeletal rearrangements 
      and activation of Cdc42, Rac1 and N-WASP were studied in the highly metastatic 
      human breast cancer cell line MDA MB 231. These studies reveal that divergent 
      signalling occurs downstream of PI3K. The activity of PI3K was not necessary for 
      uPA-induced chemotactic responses, but those induced by EGF were entirely 
      dependent upon PI3K. Furthermore, PI3K-independent chemotactic signalling by uPA 
      was shown to involve disruption of an interaction between beta(1)-integrins and 
      N-WASP and translocation of N-WASP to the actin cytoskeleton.
FAU - Sturge, Justin
AU  - Sturge J
AD  - The Randall Centre for Molecular Mechanisms of Cell Function, New Hunt's House, 
      King's College London, Guy's Campus, London SE1 1UL, UK.
FAU - Hamelin, Jocelyne
AU  - Hamelin J
FAU - Jones, Gareth E
AU  - Jones GE
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Actins)
RN  - 0 (Integrin beta1)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (WASL protein, human)
RN  - 0 (Wiskott-Aldrich Syndrome Protein, Neuronal)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
RN  - EC 3.6.5.2 (rho GTP-Binding Proteins)
SB  - IM
MH  - Actins/metabolism
MH  - Breast Neoplasms/metabolism/pathology
MH  - Carcinoma/metabolism/pathology
MH  - *Chemotaxis/drug effects
MH  - Cytoskeleton/metabolism
MH  - Epidermal Growth Factor/pharmacology
MH  - Female
MH  - Humans
MH  - Integrin beta1/*metabolism
MH  - Nerve Tissue Proteins/*metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Protein Transport
MH  - Signal Transduction
MH  - Tumor Cells, Cultured
MH  - Urokinase-Type Plasminogen Activator/*pharmacology
MH  - Wiskott-Aldrich Syndrome Protein, Neuronal
MH  - rho GTP-Binding Proteins/metabolism
EDAT- 2002/02/28 10:00
MHDA- 2002/07/03 10:01
CRDT- 2002/02/28 10:00
PHST- 2002/02/28 10:00 [pubmed]
PHST- 2002/07/03 10:01 [medline]
PHST- 2002/02/28 10:00 [entrez]
AID - 10.1242/jcs.115.4.699 [doi]
PST - ppublish
SO  - J Cell Sci. 2002 Feb 15;115(Pt 4):699-711. doi: 10.1242/jcs.115.4.699.