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Article

AQP3 Increases Intercellular Cohesion in NSCLC A549 Cell Spheroids through Exploratory Cell Protrusions

by 1,†, 1,2,*,† and 1,*
1
Cellular Reprogramming and Embryo Biotechnology Laboratory, Dental Research Institute, School of Dentistry, Seoul National University, Seoul 08826, Korea
2
Samsung Medical Center, Samsung Biomedical Research Institute, School of Medicine, Sungkyunkwan University, Seoul 06351, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this study.
Academic Editor: Luba Hunáková
Int. J. Mol. Sci. 2021, 22(8), 4287; https://doi.org/10.3390/ijms22084287
Received: 21 March 2021 / Revised: 16 April 2021 / Accepted: 17 April 2021 / Published: 20 April 2021
(This article belongs to the Special Issue Attacking Cancer Progression and Metastasis 2.0)
Tumor cell aggregation is critical for cell survival following the loss of extracellular matrix attachment and dissemination. However, the underlying mechanotransduction of clustering solitary tumor cells is poorly understood, especially in non-small cell lung cancers (NSCLC). Here, we examined whether cell surface protrusions played an important role in facilitating the physical contact between floating cells detached from a substrate. We employed poly-2-hydroxyethyl methacrylate-based 3D culture methods to mimic in vivo tumor cell cluster formation. The suprastructural analysis of human NSCLC A549 cell spheroids showed that finger-like protrusions clung together via the actin cytoskeleton. Time-lapse holotomography demonstrated that the finger-like protrusions of free-floating cells in 3D culture displayed exploratory coalescence. Global gene expression analysis demonstrated that the genes in the organic hydroxyl transport were particularly enriched in the A549 cell spheroids. Particularly, the knockdown of the water channel aquaporin 3 gene (AQP3) impaired multicellular aggregate formation in 3D culture through the rearrangement of the actomyosin cytoskeleton. Moreover, the cells with reduced levels of AQP3 decreased their transmigration. Overall, these data indicate that cell detachment-upregulated AQP3 contributes to cell surface protrusions through actomyosin cytoskeleton remodeling, causing the aggressive aggregation of free-floating cells dependent on the property of the substratum and collective metastasis. View Full-Text
Keywords: AQP3; aggregation; collective metastasis; NSCLC; lung cancer AQP3; aggregation; collective metastasis; NSCLC; lung cancer
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MDPI and ACS Style

Min, S.; Choe, C.; Roh, S. AQP3 Increases Intercellular Cohesion in NSCLC A549 Cell Spheroids through Exploratory Cell Protrusions. Int. J. Mol. Sci. 2021, 22, 4287. https://doi.org/10.3390/ijms22084287

AMA Style

Min S, Choe C, Roh S. AQP3 Increases Intercellular Cohesion in NSCLC A549 Cell Spheroids through Exploratory Cell Protrusions. International Journal of Molecular Sciences. 2021; 22(8):4287. https://doi.org/10.3390/ijms22084287

Chicago/Turabian Style

Min, Sol, Chungyoul Choe, and Sangho Roh. 2021. "AQP3 Increases Intercellular Cohesion in NSCLC A549 Cell Spheroids through Exploratory Cell Protrusions" International Journal of Molecular Sciences 22, no. 8: 4287. https://doi.org/10.3390/ijms22084287

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