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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 ; Hill, Eric ; Nagel, David ; Bill, Roslyn ; Dunmore, Simon ; Armesilla, Angel ; Gross, Stephane ; Carmichael, Amtul ... show 2 more
Arif, Muhammad
Kitchen, Philip
Conner, Matthew
Hill, Eric
Nagel, David
Bill, Roslyn
Dunmore, Simon
Armesilla, Angel
Gross, Stephane
Carmichael, Amtul
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2018-05-21
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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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Arif, M., Kitchen, P., Conner, M., Hill, E., Nagel, D., Bill, R., Dunmore, S., Armesilla, A., Gross, S., Carmichael, A., Conner, A., and Brown, J. (2018) 'Downregulation of aquaporin 3 inhibits cellular proliferation, migration and invasion in the MDA‑MB‑231 breast cancer cell line', Oncology Letters, 16 (1) pp. 713-720
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Journal article
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en
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1792-1074