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Aquaglyceroporin-3’s expression and cellular localization is differentially modulated by hypoxia in prostate cancer cell lines

de Almeida, Andreia ORCID:, Parthimos, Dimitris ORCID:, Dew, Holly, Smart, Oliver, Wiltshire, Marie and Errington, Rachel J. ORCID: 2021. Aquaglyceroporin-3’s expression and cellular localization is differentially modulated by hypoxia in prostate cancer cell lines. Cells 10 (4) , 838. 10.3390/cells10040838

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Aquaporins are required by cells to enable fast adaptation to volume and osmotic changes, as well as microenvironmental metabolic stimuli. Aquaglyceroporins play a crucial role in supplying cancer cells with glycerol for metabolic needs. Here, we show that AQP3 is differentially expressed in cells of a prostate cancer panel. AQP3 is located at the cell membrane and cytoplasm of LNCaP cell while being exclusively expressed in the cytoplasm of Du145 and PC3 cells. LNCaP cells show enhanced hypoxia growth; Du145 and PC3 cells display stress factors, indicating a crucial role for AQP3 at the plasma membrane in adaptation to hypoxia. Hypoxia, both acute and chronic affected AQP3′s cellular localization. These outcomes were validated using a machine learning classification approach of the three cell lines and of the six normoxic or hypoxic conditions. Classifiers trained on morphological features derived from cytoskeletal and nuclear labeling alongside corresponding texture features could uniquely identify each individual cell line and the corresponding hypoxia exposure. Cytoskeletal features were 70–90% accurate, while nuclear features allowed for 55–70% accuracy. Cellular texture features (73.9% accuracy) were a stronger predictor of the hypoxic load than the AQP3 distribution (60.3%).

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Additional Information: This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// 4.0/).
Publisher: MDPI
ISSN: 2073-4409
Funders: Wellcome Trust
Date of First Compliant Deposit: 20 April 2021
Date of Acceptance: 7 April 2021
Last Modified: 08 May 2023 05:48

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