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NKCC1 Regulates Migration Ability of Glioblastoma Cells by Modulation of Actin Dynamics and Interacting with Cofilin

Glioblastoma (GBM) is the most aggressive primary brain tumor in adults. The mechanisms that confer GBM cells their invasive behavior are poorly understood. The electroneutral Na(+)-K(+)-2Cl(−) co-transporter 1 (NKCC1) is an important cell volume regulator that participates in cell migration. We hav...

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Autores principales: Schiapparelli, Paula, Guerrero-Cazares, Hugo, Magaña-Maldonado, Roxana, Hamilla, Susan M., Ganaha, Sara, Goulin Lippi Fernandes, Eric, Huang, Chuan-Hsiang, Aranda-Espinoza, Helim, Devreotes, Peter, Quinones-Hinojosa, Alfredo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5514434/
https://www.ncbi.nlm.nih.gov/pubmed/28679472
http://dx.doi.org/10.1016/j.ebiom.2017.06.020
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author Schiapparelli, Paula
Guerrero-Cazares, Hugo
Magaña-Maldonado, Roxana
Hamilla, Susan M.
Ganaha, Sara
Goulin Lippi Fernandes, Eric
Huang, Chuan-Hsiang
Aranda-Espinoza, Helim
Devreotes, Peter
Quinones-Hinojosa, Alfredo
author_facet Schiapparelli, Paula
Guerrero-Cazares, Hugo
Magaña-Maldonado, Roxana
Hamilla, Susan M.
Ganaha, Sara
Goulin Lippi Fernandes, Eric
Huang, Chuan-Hsiang
Aranda-Espinoza, Helim
Devreotes, Peter
Quinones-Hinojosa, Alfredo
author_sort Schiapparelli, Paula
collection PubMed
description Glioblastoma (GBM) is the most aggressive primary brain tumor in adults. The mechanisms that confer GBM cells their invasive behavior are poorly understood. The electroneutral Na(+)-K(+)-2Cl(−) co-transporter 1 (NKCC1) is an important cell volume regulator that participates in cell migration. We have shown that inhibition of NKCC1 in GBM cells leads to decreased cell migration, in vitro and in vivo. We now report on the role of NKCC1 on cytoskeletal dynamics. We show that GBM cells display a significant decrease in F-actin content upon NKCC1 knockdown (NKCC1-KD). To determine the potential actin-regulatory mechanisms affected by NKCC1 inhibition, we studied NKCC1 protein interactions. We found that NKCC1 interacts with the actin-regulating protein Cofilin-1 and can regulate its membrane localization. Finally, we analyzed whether NKCC1 could regulate the activity of the small Rho-GTPases RhoA and Rac1. We observed that the active forms of RhoA and Rac1 were decreased in NKCC1-KD cells. In summary, we report that NKCC1 regulates GBM cell migration by modulating the cytoskeleton through multiple targets including F-actin regulation through Cofilin-1 and RhoGTPase activity. Due to its essential role in cell migration NKCC1 may serve as a specific therapeutic target to decrease cell invasion in patients with primary brain cancer.
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spelling pubmed-55144342017-07-27 NKCC1 Regulates Migration Ability of Glioblastoma Cells by Modulation of Actin Dynamics and Interacting with Cofilin Schiapparelli, Paula Guerrero-Cazares, Hugo Magaña-Maldonado, Roxana Hamilla, Susan M. Ganaha, Sara Goulin Lippi Fernandes, Eric Huang, Chuan-Hsiang Aranda-Espinoza, Helim Devreotes, Peter Quinones-Hinojosa, Alfredo EBioMedicine Research Paper Glioblastoma (GBM) is the most aggressive primary brain tumor in adults. The mechanisms that confer GBM cells their invasive behavior are poorly understood. The electroneutral Na(+)-K(+)-2Cl(−) co-transporter 1 (NKCC1) is an important cell volume regulator that participates in cell migration. We have shown that inhibition of NKCC1 in GBM cells leads to decreased cell migration, in vitro and in vivo. We now report on the role of NKCC1 on cytoskeletal dynamics. We show that GBM cells display a significant decrease in F-actin content upon NKCC1 knockdown (NKCC1-KD). To determine the potential actin-regulatory mechanisms affected by NKCC1 inhibition, we studied NKCC1 protein interactions. We found that NKCC1 interacts with the actin-regulating protein Cofilin-1 and can regulate its membrane localization. Finally, we analyzed whether NKCC1 could regulate the activity of the small Rho-GTPases RhoA and Rac1. We observed that the active forms of RhoA and Rac1 were decreased in NKCC1-KD cells. In summary, we report that NKCC1 regulates GBM cell migration by modulating the cytoskeleton through multiple targets including F-actin regulation through Cofilin-1 and RhoGTPase activity. Due to its essential role in cell migration NKCC1 may serve as a specific therapeutic target to decrease cell invasion in patients with primary brain cancer. Elsevier 2017-06-21 /pmc/articles/PMC5514434/ /pubmed/28679472 http://dx.doi.org/10.1016/j.ebiom.2017.06.020 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Schiapparelli, Paula
Guerrero-Cazares, Hugo
Magaña-Maldonado, Roxana
Hamilla, Susan M.
Ganaha, Sara
Goulin Lippi Fernandes, Eric
Huang, Chuan-Hsiang
Aranda-Espinoza, Helim
Devreotes, Peter
Quinones-Hinojosa, Alfredo
NKCC1 Regulates Migration Ability of Glioblastoma Cells by Modulation of Actin Dynamics and Interacting with Cofilin
title NKCC1 Regulates Migration Ability of Glioblastoma Cells by Modulation of Actin Dynamics and Interacting with Cofilin
title_full NKCC1 Regulates Migration Ability of Glioblastoma Cells by Modulation of Actin Dynamics and Interacting with Cofilin
title_fullStr NKCC1 Regulates Migration Ability of Glioblastoma Cells by Modulation of Actin Dynamics and Interacting with Cofilin
title_full_unstemmed NKCC1 Regulates Migration Ability of Glioblastoma Cells by Modulation of Actin Dynamics and Interacting with Cofilin
title_short NKCC1 Regulates Migration Ability of Glioblastoma Cells by Modulation of Actin Dynamics and Interacting with Cofilin
title_sort nkcc1 regulates migration ability of glioblastoma cells by modulation of actin dynamics and interacting with cofilin
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5514434/
https://www.ncbi.nlm.nih.gov/pubmed/28679472
http://dx.doi.org/10.1016/j.ebiom.2017.06.020
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