Dynamic actin remodeling during epithelial–mesenchymal transition depends on increased moesin expression

Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA.
Molecular biology of the cell (Impact Factor: 4.47). 12/2011; 22(24):4750-64. DOI: 10.1091/mbc.E11-02-0119
Source: PubMed


Remodeling of actin filaments is necessary for epithelial-mesenchymal transition (EMT); however, understanding of how this is regulated in real time is limited. We used an actin filament reporter and high-resolution live-cell imaging to analyze the regulated dynamics of actin filaments during transforming growth factor-β-induced EMT of mammary epithelial cells. Progressive changes in cell morphology were accompanied by reorganization of actin filaments from thin cortical bundles in epithelial cells to thick, parallel, contractile bundles that disassembled more slowly but remained dynamic in transdifferentiated cells. We show that efficient actin filament remodeling during EMT depends on increased expression of the ezrin/radixin/moesin (ERM) protein moesin. Cells suppressed for moesin expression by short hairpin RNA had fewer, thinner, and less stable actin bundles, incomplete morphological transition, and decreased invasive capacity. These cells also had less α-smooth muscle actin and phosphorylated myosin light chain in cortical patches, decreased abundance of the adhesion receptor CD44 at membrane protrusions, and attenuated autophosphorylation of focal adhesion kinase. Our findings suggest that increased moesin expression promotes EMT by regulating adhesion and contractile elements for changes in actin filament organization. We propose that the transciptional program driving EMT controls progressive remodeling of actin filament architectures.

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Available from: Jyoti Srivastava, Nov 26, 2014
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    • "- actin remodeling can affect the integrity of cell - cell junctions and destabilize the epithelial barrier , rendering leukocytes access to surrounding tissues . Reorganization of the actin cytoskeleton and loss of cell - cell adhesions are also seen in epithelial - mesenchymal transition , a phenomenon that occurs in fibrosis and wound healing ( Haynes et al . , 2011 ) . A significant reduction in f - actin levels in lateral wall , spiral ganglion and cochlear nerve at 3 – 7 days in vivo contrasts with an increase on this stress fibers component in the area where the electrode - analog was placed ( Figures 4 , 6 ) ."
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