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Int. J. Mol. Sci. 2018, 19(4), 1033; https://doi.org/10.3390/ijms19041033

TASK-3 Downregulation Triggers Cellular Senescence and Growth Inhibition in Breast Cancer Cell Lines

Centro de Investigaciones Médicas (CIM), Programa de Investigación Asociativa en Cáncer Gástrico (PIA-CG), Escuela de Medicina, Universidad de Talca, Talca 3460000, Chile
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Received: 28 February 2018 / Revised: 23 March 2018 / Accepted: 26 March 2018 / Published: 29 March 2018
(This article belongs to the Section Biochemistry)
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Abstract

TASK-3 potassium channels are believed to promote proliferation and survival of cancer cells, in part, by augmenting their resistance to both hypoxia and serum deprivation. While overexpression of TASK-3 is frequently observed in cancers, the understanding of its role and regulation during tumorigenesis remains incomplete. Here, we evaluated the effect of reducing the expression of TASK-3 in MDA-MB-231 and MCF-10F human mammary epithelial cell lines through small hairpin RNA (shRNA)-mediated knockdown. Our results show that knocking down TASK-3 in fully transformed MDA-MB-231 cells reduces proliferation, which was accompanied by an induction of cellular senescence and cell cycle arrest, with an upregulation of cyclin-dependent kinase (CDK) inhibitors p21 and p27. In non-tumorigenic MCF-10F cells, however, TASK-3 downregulation did not lead to senescence induction, although cell proliferation was impaired and an upregulation of CDK inhibitors was also evident. Our observations implicate TASK-3 as a critical factor in cell cycle progression and corroborate its potential as a therapeutic target in breast cancer treatment. View Full-Text
Keywords: TASK-3; two-pore domain channel; breast cancer; cell cycle; senescence; cyclin-dependent kinase inhibitors TASK-3; two-pore domain channel; breast cancer; cell cycle; senescence; cyclin-dependent kinase inhibitors
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Zúñiga, R.; Valenzuela, C.; Concha, G.; Brown, N.; Zúñiga, L. TASK-3 Downregulation Triggers Cellular Senescence and Growth Inhibition in Breast Cancer Cell Lines. Int. J. Mol. Sci. 2018, 19, 1033.

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