Differential expression of the long and truncated Hv1 isoforms in breast‐cancer cells

VENTURA, CLARA; LEON, IGNACIO ESTEBAN; ASUAJE, AGUSTIN; MARTÍN, PEDRO; ENRIQUE, NICOLAS; NÚÑEZ, MARIEL; COCCA, CLAUDIA; MILESI, VERÓNICA

JOURNAL OF CELLULAR PHYSIOLOGY

WILEY-LISS, DIV JOHN WILEY & SONS INC

Año: 2020

0021-9541

Metabolic reprogramming of cancer cells results in a high production of acidicsubstances that must be extruded to maintain tumor‐cell viability. The voltage‐gatedproton channel (Hv1) mediates highly selective effluxes of hydronium‐ion (H+) thatprevent deleterious cytoplasmic acidification. In the work described here, we demonstratedfor the first time that the amino‐terminal?truncated isoform of Hv1 ismore 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 breastcancer disease.