Aquaporin-3 and Aquaporin-5 Facilitate Migration and Cell–Cell Adhesion in Pancreatic Cancer by Modulating Cell Biomechanical Properties

Background: Aquaporins are membrane channels responsible for the bidirectional transfer of water and small non-charged solutes across cell membranes. AQP3 and AQP5 are overexpressed in pancreatic ductal adenocarcinoma, playing key roles in cell migration, proliferation, and invasion. Here, we evalua...

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Main Authors: Patrícia M. Silva, Inês V. da Silva, Maria J. Sarmento, Ítala C. Silva, Filomena A. Carvalho, Graça Soveral, Nuno C. Santos
Format: Article
Language:English
Published: MDPI AG 2022-04-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/11/8/1308
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author Patrícia M. Silva
Inês V. da Silva
Maria J. Sarmento
Ítala C. Silva
Filomena A. Carvalho
Graça Soveral
Nuno C. Santos
author_facet Patrícia M. Silva
Inês V. da Silva
Maria J. Sarmento
Ítala C. Silva
Filomena A. Carvalho
Graça Soveral
Nuno C. Santos
author_sort Patrícia M. Silva
collection DOAJ
description Background: Aquaporins are membrane channels responsible for the bidirectional transfer of water and small non-charged solutes across cell membranes. AQP3 and AQP5 are overexpressed in pancreatic ductal adenocarcinoma, playing key roles in cell migration, proliferation, and invasion. Here, we evaluated AQP3 and AQP5 involvement in cell biomechanical properties, cell–cell adhesion, and cell migration, following a loss-of-function strategy on BxPC-3 cells. Results: Silencing of AQP3 and AQP5 was functionally validated by reduced membrane permeability and had implications on cell migration, slowing wound recovery. Moreover, silenced AQP5 and AQP3/5 cells showed higher membrane fluidity. Biomechanical and morphological changes were assessed by atomic force microscopy (AFM), revealing AQP5 and AQP3/5 silenced cells with a lower stiffness than their control. Through cell–cell adhesion measurements, the work (energy) necessary to detach two cells was found to be lower for AQP-silenced cells than control, showing that these AQPs have implications on cell–cell adhesion. Conclusion: These findings highlight AQP3 and AQP5 involvement in the biophysical properties of cell membranes, whole cell biomechanical properties, and cell–cell adhesion, thus having potential implication in the settings of tumor development.
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spelling doaj.art-3c518c557c334efcba5541a24e74d5bb2023-12-01T01:14:01ZengMDPI AGCells2073-44092022-04-01118130810.3390/cells11081308Aquaporin-3 and Aquaporin-5 Facilitate Migration and Cell–Cell Adhesion in Pancreatic Cancer by Modulating Cell Biomechanical PropertiesPatrícia M. Silva0Inês V. da Silva1Maria J. Sarmento2Ítala C. Silva3Filomena A. Carvalho4Graça Soveral5Nuno C. Santos6Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, PortugalResearch Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, PortugalInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, PortugalInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, PortugalInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, PortugalResearch Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, PortugalInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, PortugalBackground: Aquaporins are membrane channels responsible for the bidirectional transfer of water and small non-charged solutes across cell membranes. AQP3 and AQP5 are overexpressed in pancreatic ductal adenocarcinoma, playing key roles in cell migration, proliferation, and invasion. Here, we evaluated AQP3 and AQP5 involvement in cell biomechanical properties, cell–cell adhesion, and cell migration, following a loss-of-function strategy on BxPC-3 cells. Results: Silencing of AQP3 and AQP5 was functionally validated by reduced membrane permeability and had implications on cell migration, slowing wound recovery. Moreover, silenced AQP5 and AQP3/5 cells showed higher membrane fluidity. Biomechanical and morphological changes were assessed by atomic force microscopy (AFM), revealing AQP5 and AQP3/5 silenced cells with a lower stiffness than their control. Through cell–cell adhesion measurements, the work (energy) necessary to detach two cells was found to be lower for AQP-silenced cells than control, showing that these AQPs have implications on cell–cell adhesion. Conclusion: These findings highlight AQP3 and AQP5 involvement in the biophysical properties of cell membranes, whole cell biomechanical properties, and cell–cell adhesion, thus having potential implication in the settings of tumor development.https://www.mdpi.com/2073-4409/11/8/1308aquaporinsaquaglyceroporinshydrogen peroxidepancreatic cancercell–cell adhesionmembrane fluidity
spellingShingle Patrícia M. Silva
Inês V. da Silva
Maria J. Sarmento
Ítala C. Silva
Filomena A. Carvalho
Graça Soveral
Nuno C. Santos
Aquaporin-3 and Aquaporin-5 Facilitate Migration and Cell–Cell Adhesion in Pancreatic Cancer by Modulating Cell Biomechanical Properties
Cells
aquaporins
aquaglyceroporins
hydrogen peroxide
pancreatic cancer
cell–cell adhesion
membrane fluidity
title Aquaporin-3 and Aquaporin-5 Facilitate Migration and Cell–Cell Adhesion in Pancreatic Cancer by Modulating Cell Biomechanical Properties
title_full Aquaporin-3 and Aquaporin-5 Facilitate Migration and Cell–Cell Adhesion in Pancreatic Cancer by Modulating Cell Biomechanical Properties
title_fullStr Aquaporin-3 and Aquaporin-5 Facilitate Migration and Cell–Cell Adhesion in Pancreatic Cancer by Modulating Cell Biomechanical Properties
title_full_unstemmed Aquaporin-3 and Aquaporin-5 Facilitate Migration and Cell–Cell Adhesion in Pancreatic Cancer by Modulating Cell Biomechanical Properties
title_short Aquaporin-3 and Aquaporin-5 Facilitate Migration and Cell–Cell Adhesion in Pancreatic Cancer by Modulating Cell Biomechanical Properties
title_sort aquaporin 3 and aquaporin 5 facilitate migration and cell cell adhesion in pancreatic cancer by modulating cell biomechanical properties
topic aquaporins
aquaglyceroporins
hydrogen peroxide
pancreatic cancer
cell–cell adhesion
membrane fluidity
url https://www.mdpi.com/2073-4409/11/8/1308
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