Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.4.3.13 (
lysyl oxidase
)
1,248
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We have previously demonstrated that
lysyl oxidase
(
LOX
) is expressed in invasive breast cancer cells compared to poorly invasive cells. Additionally, we have recently shown that
LOX
regulates cell migration, a key step in the invasion process, through a hydrogen peroxide-dependent mechanism involving the focal adhesion kinase (FAK)/Src signaling complex. Here we further elucidate the role of
LOX
in cell motility/migration by examining the role of
LOX
in actin filament polymerization. We demonstrate that inhibition of
LOX
leads to an increase in phalloidin staining, directly associated with an increase in actin stress fiber formation. This increase in staining was confirmed by activity assays showing an increase in Rho activity with decreased
LOX
activity. Additionally, Rac and Cdc42 activity decreased with the reduction in
LOX
activity. Taken together, these data demonstrate a loss of a motogenic phenotype with decreased
LOX
activity. Finally, in order to elucidate the mechanism by which
LOX
regulates actin polymerization, we have demonstrated that
LOX
facilitates
p130
(Cas) phosphorylation, which allows for the binding to CAS related kinase (Crk) and formation of the
p130
(Cas)/Crk/DOCK180 signaling complex. Formation of this complex leads to an increase in Rac-GTP, which decreases actin stress fiber formation and increases formation of lamellipodium. These data demonstrate that
LOX
regulates cell motility/migration through changes in actin filament polymerization, which involve the regulation of the
p130
(Cas)/Crk/DOCK180 signaling pathway. Elucidating the role of
LOX
in the regulation of cell motility will allow the development of more effective therapeutic strategies to treat invasive/metastatic breast cancer.
...
PMID:Lysyl oxidase regulates actin filament formation through the p130(Cas)/Crk/DOCK180 signaling complex. 1644 Mar 29
