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Differential expression of the long and truncated Hv1 isoforms in breast-cancer cells.
J Cell Physiol. 2020 Apr 23 [Online ahead of print]JC

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.

Authors+Show Affiliations

Instituto de Estudios Inmunológicos y Fisiopatológicos (IIFP), CONICET-UNLP, La Plata, Buenos Aires, Argentina. Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.Centro de Química Inorgánica (CEQUINOR), CONICET-UNLP, La Plata, Buenos Aires, Argentina.Instituto de Estudios Inmunológicos y Fisiopatológicos (IIFP), CONICET-UNLP, La Plata, Buenos Aires, Argentina.Instituto de Estudios Inmunológicos y Fisiopatológicos (IIFP), CONICET-UNLP, La Plata, Buenos Aires, Argentina.Instituto de Estudios Inmunológicos y Fisiopatológicos (IIFP), CONICET-UNLP, La Plata, Buenos Aires, Argentina.Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina. Instituto de Química y Fisicoquímica Biológica (IQUIFIB), CONICET-UBA, Buenos Aires, Argentina.Instituto de Estudios Inmunológicos y Fisiopatológicos (IIFP), CONICET-UNLP, La Plata, Buenos Aires, Argentina.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32324259

Citation

Ventura, Clara, et al. "Differential Expression of the Long and Truncated Hv1 Isoforms in Breast-cancer Cells." Journal of Cellular Physiology, 2020.
Ventura C, Leon IE, Asuaje A, et al. Differential expression of the long and truncated Hv1 isoforms in breast-cancer cells. J Cell Physiol. 2020.
Ventura, C., Leon, I. E., Asuaje, A., Martín, P., Enrique, N., Núñez, M., Cocca, C., & Milesi, V. (2020). Differential expression of the long and truncated Hv1 isoforms in breast-cancer cells. Journal of Cellular Physiology. https://doi.org/10.1002/jcp.29719
Ventura C, et al. Differential Expression of the Long and Truncated Hv1 Isoforms in Breast-cancer Cells. J Cell Physiol. 2020 Apr 23; PubMed PMID: 32324259.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential expression of the long and truncated Hv1 isoforms in breast-cancer cells. AU - Ventura,Clara, AU - Leon,Ignacio Esteban, AU - Asuaje,Agustin, AU - Martín,Pedro, AU - Enrique,Nicolas, AU - Núñez,Mariel, AU - Cocca,Claudia, AU - Milesi,Verónica, Y1 - 2020/04/23/ PY - 2019/08/13/received PY - 2020/03/31/revised PY - 2020/04/01/accepted PY - 2020/4/24/pubmed PY - 2020/4/24/medline PY - 2020/4/24/entrez KW - Hv1 KW - Warburg effect KW - breast cancer KW - pHi JF - Journal of cellular physiology JO - J. Cell. Physiol. N2 - 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. SN - 1097-4652 UR - https://www.unboundmedicine.com/medline/citation/32324259/Differential_expression_of_the_long_and_truncated_Hv1_isoforms_in_breast-cancer_cells L2 - https://doi.org/10.1002/jcp.29719 DB - PRIME DP - Unbound Medicine ER -
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