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 have show...
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doaj-0c66a687ff5e4983bb846ecf3c246f602020-11-25T01:38:17ZengElsevierEBioMedicine2352-39642017-07-0121C9410310.1016/j.ebiom.2017.06.020NKCC1 Regulates Migration Ability of Glioblastoma Cells by Modulation of Actin Dynamics and Interacting with CofilinPaula Schiapparelli0Hugo Guerrero-Cazares1Roxana Magaña-Maldonado2Susan M. Hamilla3Sara Ganaha4Eric Goulin Lippi Fernandes5Chuan-Hsiang Huang6Helim Aranda-Espinoza7Peter Devreotes8Alfredo Quinones-Hinojosa9Department of Neurosurgery, Mayo Clinic College of Medicine, Jacksonville, FL, United StatesDepartment of Neurosurgery, Mayo Clinic College of Medicine, Jacksonville, FL, United StatesNeuroimmunology and Neurooncology Unit, The National Institute of Neurology and Neurosurgery (NINN), Mexico City, MexicoFischell Department of Bioengineering, University of Maryland, College Park, MD, United StatesDepartment of Neurosurgery, Mayo Clinic College of Medicine, Jacksonville, FL, United StatesDepartment of Neurosurgery, Mayo Clinic College of Medicine, Jacksonville, FL, United StatesDepartment of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesFischell Department of Bioengineering, University of Maryland, College Park, MD, United StatesDepartment of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Neurosurgery, Mayo Clinic College of Medicine, Jacksonville, FL, United StatesGlioblastoma (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.http://www.sciencedirect.com/science/article/pii/S2352396417302554GlioblastomaNKCC1Actin cytoskeletonCell migration |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Paula Schiapparelli Hugo Guerrero-Cazares Roxana Magaña-Maldonado Susan M. Hamilla Sara Ganaha Eric Goulin Lippi Fernandes Chuan-Hsiang Huang Helim Aranda-Espinoza Peter Devreotes Alfredo Quinones-Hinojosa |
spellingShingle |
Paula Schiapparelli Hugo Guerrero-Cazares Roxana Magaña-Maldonado Susan M. Hamilla Sara Ganaha Eric Goulin Lippi Fernandes Chuan-Hsiang Huang Helim Aranda-Espinoza Peter Devreotes Alfredo Quinones-Hinojosa NKCC1 Regulates Migration Ability of Glioblastoma Cells by Modulation of Actin Dynamics and Interacting with Cofilin EBioMedicine Glioblastoma NKCC1 Actin cytoskeleton Cell migration |
author_facet |
Paula Schiapparelli Hugo Guerrero-Cazares Roxana Magaña-Maldonado Susan M. Hamilla Sara Ganaha Eric Goulin Lippi Fernandes Chuan-Hsiang Huang Helim Aranda-Espinoza Peter Devreotes Alfredo Quinones-Hinojosa |
author_sort |
Paula Schiapparelli |
title |
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_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_sort |
nkcc1 regulates migration ability of glioblastoma cells by modulation of actin dynamics and interacting with cofilin |
publisher |
Elsevier |
series |
EBioMedicine |
issn |
2352-3964 |
publishDate |
2017-07-01 |
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. |
topic |
Glioblastoma NKCC1 Actin cytoskeleton Cell migration |
url |
http://www.sciencedirect.com/science/article/pii/S2352396417302554 |
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