Differential expression of the long and truncated Hv1 isoforms in breast‐cancer cells
- 23 April 2020
- journal article
- research article
- Published by Wiley in Journal of Cellular Physiology
- Vol. 235 (11), 8757-8767
- https://doi.org/10.1002/jcp.29719
Abstract
Metabolic reprogramming of cancer cells results in a high production of acidic substances that must be extruded to maintain tumor‐cell viability. The voltage‐gated proton channel (Hv1) mediates highly selective effluxes of hydronium‐ion (H+) that prevent deleterious cytoplasmic acidification. In the work described here, we demonstrated for the first time that the amino‐terminal–truncated isoform of Hv1 is more highly expressed in tumorigenic breast‐cancer‐cell lines than in nontumorigenic breast cells. With respect to Hv1 function, we observed that pharmacologic inhibition of that channel, mediated by the specific blocker 5‐chloro‐2‐guanidinobenzimidazole, produced a drop in intracellular pH and a decrease in cell viability, both in monolayer and in three‐dimensional cultures, and adversely affected the cell‐cycle in tumorigenic breast cells without altering the cycling of nontumorigenic cells. In conclusion, our results demonstrated that the Hv1 channel could be a potential tool both as a biomarker and as a therapeutic target in breast‐cancer disease.Funding Information
- Universidad Nacional de La Plata (11X/690)
- Agencia Nacional de Promoción Científica y Tecnológica (PICT2014‐2223, PICT2016‐1574)
- Consejo Nacional de Investigaciones Científicas y Técnicas (PIP‐00340)
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