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PMID: 15337778 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Phospholipase C and cofilin are required for carcinoma cell directionality in response to EGF stimulation.

The Journal of cell biology ·Vol. 166 ·No. 5 ·2004-08-30 ·Pages 697-708

Mouneimne G, Soon L, DesMarais V, Sidani M, Song X, Yip SC, Ghosh M, Eddy R, Backer JM, Condeelis J

Abstract

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.

MeSH Terms
Actin Cytoskeleton/drug effects,metabolism Actin Depolymerizing Factors Actins/biosynthesis,drug effects Animals Antibodies/pharmacology Carcinoma/metabolism,pathology Cell Line, Tumor Chemotaxis/drug effects,physiology Enzyme Inhibitors/pharmacology Epidermal Growth Factor/metabolism,pharmacology Microfilament Proteins/drug effects,genetics,physiology Neoplasm Metastasis/physiopathology Phosphatidylinositol 3-Kinases/drug effects,metabolism Pseudopodia/drug effects,metabolism,ultrastructure RNA Interference Rats Type C Phospholipases/drug effects,metabolism
Chemicals
Actin Depolymerizing Factors Actins Antibodies Enzyme Inhibitors Microfilament Proteins Epidermal Growth Factor Phosphatidylinositol 3-Kinases Type C Phospholipases
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Mouneimne Ghassan
Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461, USA. gmouneim@aecom.yu.edu
Soon Lilian
DesMarais Vera
Sidani Mazen
Song Xiaoyan
Yip Shu-Chin
Ghosh Mousumi
Eddy Robert
Backer Jonathan M
Condeelis John
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200405156
Email
gmouneim@aecom.yu.edu
Published
2004-08-30
Pages
697-708
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2172433
Subset
IM
Grants
NCI NIH HHS · P01 CA100324 · United States
NIGMS NIH HHS · R01 GM038511 · United States
NCI NIH HHS · CA100324 · United States
NIGMS NIH HHS · GM38511 · United States
External Links
PubMed source DOI: 10.1083/jcb.200405156 PMC Full Text View journal details
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