Phospholipase C and Cofilin Are Required for Carcinoma Cell Directionality in Response to EGF Stimulation

• Published in: The Journal of cell biology Vol. 166; no. 5; pp. 697 - 708
• Main Authors: Mouneimne, Ghassan, Soon, Lilian, DesMarais, Vera, Sidani, Mazen, Song, Xiaoyan, Yip, Shu-Chin, Ghosh, Mousumi, Eddy, Robert, Backer, Jonathan M., Condeelis, John
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 30-08-2004; The Rockefeller University Press
• Subjects: Actin Cytoskeleton - drug effects; Actin Cytoskeleton - metabolism; Actin Depolymerizing Factors; Actins; Actins - biosynthesis; Actins - drug effects; Animals; Antibodies; Antibodies - pharmacology; Cancer; Carcinoma; Carcinoma - metabolism; Carcinoma - pathology; Cell Line, Tumor; Cell lines; Cell motility; Cells; Chemotaxis; Chemotaxis - drug effects; Chemotaxis - physiology; Enzyme Inhibitors - pharmacology; Enzymes; Epidermal Growth Factor - metabolism; Epidermal Growth Factor - pharmacology; Microfilament Proteins - drug effects; Microfilament Proteins - genetics; Microfilament Proteins - physiology; Neoplasm Metastasis - physiopathology; Phosphatidylinositol 3-Kinases - drug effects; Phosphatidylinositol 3-Kinases - metabolism; Polymerization; Pseudopodia - drug effects; Pseudopodia - metabolism; Pseudopodia - ultrastructure; Rats; RNA Interference; Skin; Small interfering RNA; Type C Phospholipases - drug effects; Type C Phospholipases - metabolism
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.200405156

The epidermal growth factor (EGF)-induced increase in free barbed ends, resulting in actin polymerization at the leading edge of the lamellipodium in carcinoma cells, occurs as two transients: an early one at 1 min and a late one at 3 min. Our results reveal that phospholipase (PLC) is required for triggering the early barbed end transient. Phosphoinositide-3 kinase selectively regulates the late barbed end transient. Inhibition of PLC inhibits cofilin activity in cells during the early transient, delays the initiation of protrusions, and inhibits the ability of cells to sense a gradient of EGF. Suppression of cofilin, using either small interfering RNA silencing or function-blocking antibodies, selectively inhibits the early transient. Therefore, our results demonstrate that the early PLC and cofilin-dependent barbed end transient is required for the initiation of protrusions and is involved in setting the direction of cell movement in response to EGF.