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

Muhammad Arif, Philip Kitchen, Matthew Conner, Eric Hill, David Nagel, Roslyn Bill, Simon Dunmore, Angel Armesilla, Stephane Gross, Amtul Carmichael, Alex Conner, James Brown

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)713-720
JournalOncology Letters
Volume16
Issue number1
Early online date21 May 2018
DOIs
Publication statusPublished - May 2018

Bibliographical note

© Arif et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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