N-WASP activation by a β1-integrin-dependent mechanism supports PI3K-independent chemotaxis stimulated by urokinase-type plasminogen activator
作者： Jocelyne Hamelin , Gareth E. Jones , Justin Sturge
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摘要: Urokinase-type plasminogen activator (uPA)-uPA receptor (uPAR) and epidermal growth factor (EGF)-EGF (EGFR) expression is highly correlated with breast cancer metastasis. Phosphoinositide 3-kinase (PI3K), small Rho GTPases, such as Cdc42 and Rac1, neuronal Wiskott Aldrich syndrome protein (N-WASP) are key effectors that regulate dynamic changes in the actin cytoskeleton cell migration. uPA- EGF-stimulated chemotaxis, cytoskeletal rearrangements activation of Cdc42, Rac1 N-WASP were studied in the highly metastatic human line MDA MB 231. These studies reveal divergent signalling occurs downstream PI3K. The activity PI3K was not necessary for uPA-induced chemotactic responses, but those induced by EGF were entirely dependent upon Furthermore, PI3K-independent uPA shown to involve disruption of an interaction between β 1 -integrins and translocation cytoskeleton.
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