N-WASP activation by a β1-integrin-dependent mechanism supports PI3K-independent chemotaxis stimulated by urokinase-type plasminogen activator

Sturge, Justin; Hamelin, Joceleyne; Jones, Gareth

Abstract

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 β1-integrins and N-WASP and translocation of N-WASP to the actin cytoskeleton.

Citation

Sturge, J., Hamelin, J., & Jones, G. (2002). N-WASP activation by a β1-integrin-dependent mechanism supports PI3K-independent chemotaxis stimulated by urokinase-type plasminogen activator. Journal of cell science, 115(4), 699-711

• Journal Article Type: Article
• Acceptance Date: Nov 12, 2001
• Online Publication Date: Feb 15, 2002
• Publication Date: Feb 15, 2002
• Deposit Date: Jun 27, 2019
• Print ISSN: 0021-9533
• Publisher: The Company of Biologists
• Peer Reviewed: Peer Reviewed
• Volume: 115
• Issue: 4
• Pages: 699-711
• Keywords: Cell migration; Chemotaxis; Phosphoinositide 3-kinase; Rho GTPases; Actin; Cytoskeleton
• Public URL: https://hull-repository.worktribe.com/output/2006689
• Publisher URL: https://jcs.biologists.org/content/115/4/699