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

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.

• 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
• Journal: Oncology letters (Oncol Lett) Vol. 16 Issue 1 Pg. 713-720 (Jul 2018) ISSN: 1792-1074 [Print] Greece
• PMID: 29963136 (Publication Type: Journal Article)