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The Activity of K(V)11.1 Potassium Channel Modulates F-Actin Organization During Cell Migration of Pancreatic Ductal Adenocarcinoma Cells
Cell migration exerts a pivotal role in tumor progression, underlying cell invasion and metastatic spread. The cell migratory program requires f-actin re-organization, generally coordinated with the assembly of focal adhesions. Ion channels are emerging actors in regulating cell migration, through d...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406627/ https://www.ncbi.nlm.nih.gov/pubmed/30678127 http://dx.doi.org/10.3390/cancers11020135 |
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author | Manoli, Sagar Coppola, Stefano Duranti, Claudia Lulli, Matteo Magni, Lara Kuppalu, Nirmala Nielsen, Nikolaj Schmidt, Thomas Schwab, Albrecht Becchetti, Andrea Arcangeli, Annarosa |
author_facet | Manoli, Sagar Coppola, Stefano Duranti, Claudia Lulli, Matteo Magni, Lara Kuppalu, Nirmala Nielsen, Nikolaj Schmidt, Thomas Schwab, Albrecht Becchetti, Andrea Arcangeli, Annarosa |
author_sort | Manoli, Sagar |
collection | PubMed |
description | Cell migration exerts a pivotal role in tumor progression, underlying cell invasion and metastatic spread. The cell migratory program requires f-actin re-organization, generally coordinated with the assembly of focal adhesions. Ion channels are emerging actors in regulating cell migration, through different mechanisms. We studied the role of the voltage dependent potassium channel K(V)11.1 on cell migration of pancreatic ductal adenocarcinoma (PDAC) cells, focusing on its effects on f-actin organization and dynamics. Cells were cultured either on fibronectin (FN) or on a desmoplastic matrix (DM) with the addition of a conditioned medium produced by pancreatic stellate cells (PSC) maintained in hypoxia (Hypo-PSC-CM), to better mimic the PDAC microenvironment. K(V)11.1 was essential to maintain stress fibers in a less organized arrangement in cells cultured on FN. When PDAC cells were cultured on DM plus Hypo-PSC-CM, K(V)11.1 activity determined the organization of cortical f-actin into sparse and long filopodia, and allowed f-actin polymerization at a high speed. In both conditions, blocking K(V)11.1 impaired PDAC cell migration, and, on cells cultured onto FN, the effect was accompanied by a decrease of basal intracellular Ca(2+) concentration. We conclude that K(V)11.1 is implicated in sustaining pro-metastatic signals in pancreatic cancer, through a reorganization of f-actin in stress fibers and a modulation of filopodia formation and dynamics. |
format | Online Article Text |
id | pubmed-6406627 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-64066272019-03-21 The Activity of K(V)11.1 Potassium Channel Modulates F-Actin Organization During Cell Migration of Pancreatic Ductal Adenocarcinoma Cells Manoli, Sagar Coppola, Stefano Duranti, Claudia Lulli, Matteo Magni, Lara Kuppalu, Nirmala Nielsen, Nikolaj Schmidt, Thomas Schwab, Albrecht Becchetti, Andrea Arcangeli, Annarosa Cancers (Basel) Article Cell migration exerts a pivotal role in tumor progression, underlying cell invasion and metastatic spread. The cell migratory program requires f-actin re-organization, generally coordinated with the assembly of focal adhesions. Ion channels are emerging actors in regulating cell migration, through different mechanisms. We studied the role of the voltage dependent potassium channel K(V)11.1 on cell migration of pancreatic ductal adenocarcinoma (PDAC) cells, focusing on its effects on f-actin organization and dynamics. Cells were cultured either on fibronectin (FN) or on a desmoplastic matrix (DM) with the addition of a conditioned medium produced by pancreatic stellate cells (PSC) maintained in hypoxia (Hypo-PSC-CM), to better mimic the PDAC microenvironment. K(V)11.1 was essential to maintain stress fibers in a less organized arrangement in cells cultured on FN. When PDAC cells were cultured on DM plus Hypo-PSC-CM, K(V)11.1 activity determined the organization of cortical f-actin into sparse and long filopodia, and allowed f-actin polymerization at a high speed. In both conditions, blocking K(V)11.1 impaired PDAC cell migration, and, on cells cultured onto FN, the effect was accompanied by a decrease of basal intracellular Ca(2+) concentration. We conclude that K(V)11.1 is implicated in sustaining pro-metastatic signals in pancreatic cancer, through a reorganization of f-actin in stress fibers and a modulation of filopodia formation and dynamics. MDPI 2019-01-23 /pmc/articles/PMC6406627/ /pubmed/30678127 http://dx.doi.org/10.3390/cancers11020135 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Manoli, Sagar Coppola, Stefano Duranti, Claudia Lulli, Matteo Magni, Lara Kuppalu, Nirmala Nielsen, Nikolaj Schmidt, Thomas Schwab, Albrecht Becchetti, Andrea Arcangeli, Annarosa The Activity of K(V)11.1 Potassium Channel Modulates F-Actin Organization During Cell Migration of Pancreatic Ductal Adenocarcinoma Cells |
title | The Activity of K(V)11.1 Potassium Channel Modulates F-Actin Organization During Cell Migration of Pancreatic Ductal Adenocarcinoma Cells |
title_full | The Activity of K(V)11.1 Potassium Channel Modulates F-Actin Organization During Cell Migration of Pancreatic Ductal Adenocarcinoma Cells |
title_fullStr | The Activity of K(V)11.1 Potassium Channel Modulates F-Actin Organization During Cell Migration of Pancreatic Ductal Adenocarcinoma Cells |
title_full_unstemmed | The Activity of K(V)11.1 Potassium Channel Modulates F-Actin Organization During Cell Migration of Pancreatic Ductal Adenocarcinoma Cells |
title_short | The Activity of K(V)11.1 Potassium Channel Modulates F-Actin Organization During Cell Migration of Pancreatic Ductal Adenocarcinoma Cells |
title_sort | activity of k(v)11.1 potassium channel modulates f-actin organization during cell migration of pancreatic ductal adenocarcinoma cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406627/ https://www.ncbi.nlm.nih.gov/pubmed/30678127 http://dx.doi.org/10.3390/cancers11020135 |
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