Inflammation associated with incessant ovulation plays a key role in epithelial ovarian cancer (EOC) pathogenesis. Ion channels, such as acid-sensing ion channel-2 or ASIC2 are known to be upregulated in inflammatory conditions and may play a role in cancer cell invasion and metastasis. Previously we reported the role of phosphodiesterase 10A (PDE10) modulation of β-catenin in ovarian cancer, and are currently investigating its contribution to ovarian pathogenesis. Differential ASIC2 expression was noted with PDE10 modulation in both pre-malignant and ovarian cancer tissues. Hence, we presently report the potential role of ASIC2 in EOC development and progression as well as involvement with PDE10. ASIC2 protein is expressed across all EOC cell lines, primarily within the nucleus. Knockout of PDE10 decreased ASIC2. Conversely, ASIC2 inhibition decreased ASIC2 as well as PDE10 protein levels. ASIC2 inhibition via Diminazene also produced marked ovarian cancer death. While changes in extracellular pH did not impact ASIC2 expression, intracellular pH and calcium levels increased with ASIC inhibition. Calcium increases induced a decrease in oncogenic β-catenin. There may be a direct relationship between PDE10 and ASIC2 protein expression in EOC through convergence on a β-catenin mediated signaling pathway. This could potentially implicate ion channels, specifically ASIC2, as a link between the acidic tumor microenvironment and cancer cell signaling. It is also possible that ASIC2 plays a crucial role in acidosis-mediated tumorigenesis in ovarian cancer.
Keywords: ASIC2; Calcium channel; Ovarian cancer; PDE10; Β-catenin.
© 2025. The Author(s).