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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...

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Autores principales: Manoli, Sagar, Coppola, Stefano, Duranti, Claudia, Lulli, Matteo, Magni, Lara, Kuppalu, Nirmala, Nielsen, Nikolaj, Schmidt, Thomas, Schwab, Albrecht, Becchetti, Andrea, Arcangeli, Annarosa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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.
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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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