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Loss of γ-cytoplasmic actin triggers myofibroblast transition of human epithelial cells

Transdifferentiation of epithelial cells into mesenchymal cells and myofibroblasts plays an important role in tumor progression and tissue fibrosis. Such epithelial plasticity is accompanied by dramatic reorganizations of the actin cytoskeleton, although mechanisms underlying cytoskeletal effects on...

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Autores principales: Lechuga, Susana, Baranwal, Somesh, Li, Chao, Naydenov, Nayden G., Kuemmerle, John F., Dugina, Vera, Chaponnier, Christine, Ivanov, Andrei I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196865/
https://www.ncbi.nlm.nih.gov/pubmed/25143399
http://dx.doi.org/10.1091/mbc.E14-03-0815
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author Lechuga, Susana
Baranwal, Somesh
Li, Chao
Naydenov, Nayden G.
Kuemmerle, John F.
Dugina, Vera
Chaponnier, Christine
Ivanov, Andrei I.
author_facet Lechuga, Susana
Baranwal, Somesh
Li, Chao
Naydenov, Nayden G.
Kuemmerle, John F.
Dugina, Vera
Chaponnier, Christine
Ivanov, Andrei I.
author_sort Lechuga, Susana
collection PubMed
description Transdifferentiation of epithelial cells into mesenchymal cells and myofibroblasts plays an important role in tumor progression and tissue fibrosis. Such epithelial plasticity is accompanied by dramatic reorganizations of the actin cytoskeleton, although mechanisms underlying cytoskeletal effects on epithelial transdifferentiation remain poorly understood. In the present study, we observed that selective siRNA-mediated knockdown of γ-cytoplasmic actin (γ-CYA), but not β-cytoplasmic actin, induced epithelial-to-myofibroblast transition (EMyT) of different epithelial cells. The EMyT manifested by increased expression of α-smooth muscle actin and other contractile proteins, along with inhibition of genes responsible for cell proliferation. Induction of EMyT in γ-CYA–depleted cells depended on activation of serum response factor and its cofactors, myocardial-related transcriptional factors A and B. Loss of γ-CYA stimulated formin-mediated actin polymerization and activation of Rho GTPase, which appear to be essential for EMyT induction. Our findings demonstrate a previously unanticipated, unique role of γ-CYA in regulating epithelial phenotype and suppression of EMyT that may be essential for cell differentiation and tissue fibrosis.
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spelling pubmed-41968652014-12-30 Loss of γ-cytoplasmic actin triggers myofibroblast transition of human epithelial cells Lechuga, Susana Baranwal, Somesh Li, Chao Naydenov, Nayden G. Kuemmerle, John F. Dugina, Vera Chaponnier, Christine Ivanov, Andrei I. Mol Biol Cell Articles Transdifferentiation of epithelial cells into mesenchymal cells and myofibroblasts plays an important role in tumor progression and tissue fibrosis. Such epithelial plasticity is accompanied by dramatic reorganizations of the actin cytoskeleton, although mechanisms underlying cytoskeletal effects on epithelial transdifferentiation remain poorly understood. In the present study, we observed that selective siRNA-mediated knockdown of γ-cytoplasmic actin (γ-CYA), but not β-cytoplasmic actin, induced epithelial-to-myofibroblast transition (EMyT) of different epithelial cells. The EMyT manifested by increased expression of α-smooth muscle actin and other contractile proteins, along with inhibition of genes responsible for cell proliferation. Induction of EMyT in γ-CYA–depleted cells depended on activation of serum response factor and its cofactors, myocardial-related transcriptional factors A and B. Loss of γ-CYA stimulated formin-mediated actin polymerization and activation of Rho GTPase, which appear to be essential for EMyT induction. Our findings demonstrate a previously unanticipated, unique role of γ-CYA in regulating epithelial phenotype and suppression of EMyT that may be essential for cell differentiation and tissue fibrosis. The American Society for Cell Biology 2014-10-15 /pmc/articles/PMC4196865/ /pubmed/25143399 http://dx.doi.org/10.1091/mbc.E14-03-0815 Text en © 2014 Lechuga, Baranwal, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Lechuga, Susana
Baranwal, Somesh
Li, Chao
Naydenov, Nayden G.
Kuemmerle, John F.
Dugina, Vera
Chaponnier, Christine
Ivanov, Andrei I.
Loss of γ-cytoplasmic actin triggers myofibroblast transition of human epithelial cells
title Loss of γ-cytoplasmic actin triggers myofibroblast transition of human epithelial cells
title_full Loss of γ-cytoplasmic actin triggers myofibroblast transition of human epithelial cells
title_fullStr Loss of γ-cytoplasmic actin triggers myofibroblast transition of human epithelial cells
title_full_unstemmed Loss of γ-cytoplasmic actin triggers myofibroblast transition of human epithelial cells
title_short Loss of γ-cytoplasmic actin triggers myofibroblast transition of human epithelial cells
title_sort loss of γ-cytoplasmic actin triggers myofibroblast transition of human epithelial cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196865/
https://www.ncbi.nlm.nih.gov/pubmed/25143399
http://dx.doi.org/10.1091/mbc.E14-03-0815
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