A critical role of tropomyosins in TGF-beta regulation of the actin cytoskeleton and cell motility in epithelial cells

Bakin, A. V., Safina, A., Rinehart, C., Daroqui, C., Darbary, H., Helfman, D. M. (October 2004) A critical role of tropomyosins in TGF-beta regulation of the actin cytoskeleton and cell motility in epithelial cells. Molecular Biology of the Cell, 15 (10). pp. 4682-4694. ISSN 1059-1524

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Abstract

We have investigated transforming growth factor beta (TGF-beta)-mediated induction of actin stress fibers in normal and metastatic epithelial cells. We found that stress fiber formation requires de novo protein synthesis, p38Mapk and Smad signaling. We show that TGF-beta via Smad and p38Mapk up-regulates expression of actin-binding proteins including high-molecular-weight tropomyosins, alpha-actinin and calponin h2. We demonstrate that, among these proteins, tropomyosins are both necessary and sufficient for TGF-beta induction of stress fibers. Silencing of tropomyosins with short interfering RNAs (siRNAs) blocks stress fiber assembly, whereas ectopic expression of tropomyosins results in stress fibers. Ectopic-expression and siRNA experiments show that Smads mediate induction of tropomyosins and stress fibers. Interestingly, TGF-beta induction of stress fibers was not accompanied by changes in the levels of cofilin phosphorylation. TGF-beta induction of tropomyosins and stress fibers are significantly inhibited by Ras-ERK signaling in metastatic breast cancer cells. Inhibition of the Ras-ERK pathway restores TGF-beta induction of tropomyosins and stress fibers and thereby reduces cell motility. These results suggest that induction of tropomyosins and stress fibers play an essential role in TGF-beta control of cell motility, and the loss of this TGF-beta response is a critical step in the acquisition of metastatic phenotype by tumor cells.

Item Type: Paper
Uncontrolled Keywords: GROWTH-FACTOR-BETA RAS-TRANSFORMED FIBROBLASTS ACTIVATED PROTEIN-KINASE DOWN-REGULATION MESENCHYMAL TRANSDIFFERENTIATION SIGNAL-TRANSDUCTION TUMOR-SUPPRESSOR ONCOGENIC RAS RHO-GTPASES EXPRESSION
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
diseases & disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNAi
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell
organs, tissues, organelles, cell types and functions
CSHL Authors:
Communities: CSHL labs > Helfman lab
Depositing User: Matt Covey
Date: October 2004
Date Deposited: 04 Mar 2013 20:47
Last Modified: 04 Mar 2013 20:47
PMCID: PMC519159
Related URLs:
URI: https://repository.cshl.edu/id/eprint/27710

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