Downregulation of aquaporin 3 inhibits cellular proliferation, migration and invasion in the MDA‑MB‑231 breast cancer cell line

Arif,Muhammad; Kitchen,Philip; Conner,Matthew  T.; Hill,Eric  J.; Nagel,David; Bill,Roslyn  M.; Dunmore,Simon  J.; Armesilla,Angel L.; Gross,Stephane; Carmichael,Amtul  R.; Conner,Alex  C.; Brown,James  E.

doi:10.3892/ol.2018.8759

Downregulation of aquaporin 3 inhibits cellular proliferation, migration and invasion in the MDA‑MB‑231 breast cancer cell line

Authors:
- Muhammad Arif
- Philip Kitchen
- Matthew T. Conner
- Eric J. Hill
- David Nagel
- Roslyn M. Bill
- Simon J. Dunmore
- Angel L. Armesilla
- Stephane Gross
- Amtul R. Carmichael
- Alex C. Conner
- James E. Brown
View Affiliations

Affiliations: School of Life and Health Science, Aston University, Birmingham B4 7ET, UK, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham B15 2TT, UK, Research Institute for Healthcare Science, University of Wolverhampton, Wolverhampton WV1 1SB, UK, Cardiovascular Molecular Pharmacology Group, Research Institute in Healthcare Science, School of Pharmacy, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton WV1 1SB, UK, Aston Research Centre for Healthy Ageing and Aston Medical Research Institute, School of Life and Health Sciences, Aston University, Birmingham B4 7ET, UK
Published online on: May 21, 2018 https://doi.org/10.3892/ol.2018.8759
Pages: 713-720
Copyright: © Arif et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Aquaporins are membrane proteins that regulate cellular water flow. Recently, aquaporins have been proposed as mediators of cancer cell biology. A subset of aquaporins, referred to as aquaglyceroporins are known to facilitate the transport of glycerol. The present study describes the effect of gene knockdown of the aquaglyceroporin AQP3 on MDA‑MB‑231 breast cancer cell proliferation, migration, invasion, adherence and response to the chemotherapeutic agent 5‑fluorouracil. shRNA mediated AQP3 gene knockdown induced a 28% reduction in cellular proliferation (P<0.01), a 39% decrease in migration (P<0.0001), a 24% reduction in invasion (P<0.05) and a 25% increase in cell death at 100 µM 5‑FU (P<0.01). Analysis of cell permeability to water and glycerol revealed that MDA‑MB‑231 cells with knocked down AQP3 demonstrated a modest decrease in water permeability (17%; P<0.05) but a more marked decrease in glycerol permeability (77%; P<0.001). These results suggest that AQP3 has a role in multiple aspects of breast cancer cell pathophysiology and therefore represents a novel target for therapeutic intervention.

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