Expression and function of voltage gated proton channels (Hv1) in MDA-MB-231 cells

Area of Science:

• Oncology
• Molecular Biology
• Biophysics

Background:

• Voltage-gated proton channel 1 (Hv1) expression is reported in breast cancer and linked to poor prognosis.
• The precise mechanism of Hv1 involvement in breast cancer progression remains unclear.

Purpose of the Study:

• To investigate the functional role of Hv1 in breast cancer cell lines, specifically MDA-MB-231.
• To elucidate the mechanisms underlying Hv1's contribution to tumor growth and metastasis.

Main Methods:

• Electrophysiological recordings confirmed Hv1 channel activity in MDA-MB-231 cells.
• Hv1 expression was modulated using shRNA (knock-down) and CRISPR/Cas9 (knock-out) in MDA-MB-231 cells.
• Cell migration, H2O2 release, glycolytic rate, p-AKT activity, and CD171/LCAM-1 expression were analyzed. Xenograft tumor growth was assessed in vivo.

Main Results:

• Hv1 knock-down reduced cell migration and H2O2 release, while knock-out showed increased glycolysis and p-AKT activity.
• Hv1 knock-out cells exhibited reduced CD171/LCAM-1 expression.
• Hv1 knock-out xenograft tumors showed reduced mass and proliferation compared to wild-type, independent of oxidant production.

Conclusions:

• Hv1 plays a complex role in breast cancer, with distinct effects observed between knock-down and knock-out models.
• Hv1 deletion limits tumor growth in MDA-MB-231 cells, mediated by mechanisms involving cell adhesion molecules rather than oxidant production.
• Hv1 represents a potential therapeutic target for triple-negative breast cancer.