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

Lugar: New York; Año: 2020

0021-9541

Metabolic reprogramming of cancer Q4 cells results in a Q3 high production of acidicsubstances 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 describedhere, we demonstrated for the first time that the amino‐terminal?truncatedisoform of Hv1 is more highly expressed in tumorigenic breast‐cancer‐cell linesthan in nontumorigenic breast cells. With respect to Hv1 function, we observedthat pharmacologic inhibition of that channel, mediated by the specific blocker5‐chloro‐2‐guanidinobenzimidazole, produced a drop in intracellular pH and adecrease in cell viability, both in monolayer and in three‐dimensional cultures,and adversely affected the cell‐cycle in tumorigenic breast cells without alteringthe cycling of nontumorigenic cells. In conclusion, our results demonstrated thatthe Hv1 channel could be a potential tool both as a biomarker and as atherapeutic target in breast‐cancer disease.