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Hic-5 expression is a major indicator of cancer cell morphology, migration, and plasticity in three-dimensional matrices

The focal adhesion proteins Hic-5 and paxillin have been previously identified as key regulators of MDA-MB-231 breast cancer cell migration and morphologic mesenchymal-amoeboid plasticity in three-dimensional (3D) extracellular matrices (ECMs). However, their respective roles in other cancer cell ty...

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Autores principales: Gulvady, Anushree C., Dubois, Fatemeh, Deakin, Nicholas O., Goreczny, Gregory J., Turner, Christopher E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6080706/
https://www.ncbi.nlm.nih.gov/pubmed/29771639
http://dx.doi.org/10.1091/mbc.E18-02-0092
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author Gulvady, Anushree C.
Dubois, Fatemeh
Deakin, Nicholas O.
Goreczny, Gregory J.
Turner, Christopher E.
author_facet Gulvady, Anushree C.
Dubois, Fatemeh
Deakin, Nicholas O.
Goreczny, Gregory J.
Turner, Christopher E.
author_sort Gulvady, Anushree C.
collection PubMed
description The focal adhesion proteins Hic-5 and paxillin have been previously identified as key regulators of MDA-MB-231 breast cancer cell migration and morphologic mesenchymal-amoeboid plasticity in three-dimensional (3D) extracellular matrices (ECMs). However, their respective roles in other cancer cell types have not been evaluated. Herein, utilizing 3D cell–derived matrices and fibronectin-coated one-dimensional substrates, we show that across a variety of cancer cell lines, the level of Hic-5 expression serves as the major indicator of the cells primary morphology, plasticity, and in vitro invasiveness. Domain mapping studies reveal sites critical to the functions of both Hic-5 and paxillin in regulating phenotype, while ectopic expression of Hic-5 in cell lines with low endogenous levels of the protein is sufficient to induce a Rac1-dependent mesenchymal phenotype and, in turn, increase amoeboid-mesenchymal plasticity and invasion. We show that the activity of vinculin, when coupled to the expression of Hic-5 is required for the mesenchymal morphology in the 3D ECM. Taken together, our results identify Hic-5 as a critical modulator of tumor cell phenotype that could be utilized in predicting tumor cell migratory and invasive behavior in vivo.
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spelling pubmed-60807062018-09-30 Hic-5 expression is a major indicator of cancer cell morphology, migration, and plasticity in three-dimensional matrices Gulvady, Anushree C. Dubois, Fatemeh Deakin, Nicholas O. Goreczny, Gregory J. Turner, Christopher E. Mol Biol Cell Articles The focal adhesion proteins Hic-5 and paxillin have been previously identified as key regulators of MDA-MB-231 breast cancer cell migration and morphologic mesenchymal-amoeboid plasticity in three-dimensional (3D) extracellular matrices (ECMs). However, their respective roles in other cancer cell types have not been evaluated. Herein, utilizing 3D cell–derived matrices and fibronectin-coated one-dimensional substrates, we show that across a variety of cancer cell lines, the level of Hic-5 expression serves as the major indicator of the cells primary morphology, plasticity, and in vitro invasiveness. Domain mapping studies reveal sites critical to the functions of both Hic-5 and paxillin in regulating phenotype, while ectopic expression of Hic-5 in cell lines with low endogenous levels of the protein is sufficient to induce a Rac1-dependent mesenchymal phenotype and, in turn, increase amoeboid-mesenchymal plasticity and invasion. We show that the activity of vinculin, when coupled to the expression of Hic-5 is required for the mesenchymal morphology in the 3D ECM. Taken together, our results identify Hic-5 as a critical modulator of tumor cell phenotype that could be utilized in predicting tumor cell migratory and invasive behavior in vivo. The American Society for Cell Biology 2018-07-15 /pmc/articles/PMC6080706/ /pubmed/29771639 http://dx.doi.org/10.1091/mbc.E18-02-0092 Text en © 2018 Gulvady et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 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.
spellingShingle Articles
Gulvady, Anushree C.
Dubois, Fatemeh
Deakin, Nicholas O.
Goreczny, Gregory J.
Turner, Christopher E.
Hic-5 expression is a major indicator of cancer cell morphology, migration, and plasticity in three-dimensional matrices
title Hic-5 expression is a major indicator of cancer cell morphology, migration, and plasticity in three-dimensional matrices
title_full Hic-5 expression is a major indicator of cancer cell morphology, migration, and plasticity in three-dimensional matrices
title_fullStr Hic-5 expression is a major indicator of cancer cell morphology, migration, and plasticity in three-dimensional matrices
title_full_unstemmed Hic-5 expression is a major indicator of cancer cell morphology, migration, and plasticity in three-dimensional matrices
title_short Hic-5 expression is a major indicator of cancer cell morphology, migration, and plasticity in three-dimensional matrices
title_sort hic-5 expression is a major indicator of cancer cell morphology, migration, and plasticity in three-dimensional matrices
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6080706/
https://www.ncbi.nlm.nih.gov/pubmed/29771639
http://dx.doi.org/10.1091/mbc.E18-02-0092
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