Kca3.1 Activation Via P2y2 Purinergic Receptors Promotes Human Ovarian Cancer Cell (Skov-3) Migration

Abstract

Abstract Disorders in cell signaling mediated by ATP or histamine, activating specific membrane receptors, have been frequently associated with tumorigenesis. Among the elements of response to purinergic (and histaminergic) signaling, ion channel activation controls essential cellular processes in cancer, such as cell proliferation, motility, and death. Here, we studied the effects that ATP had on electrical properties of human ovarian adenocarcinoma cells named SKOV-3. ATP caused increase in intracellular Ca 2+ concentration ([Ca 2+ ] i ) and, concurrently, it evoked a complex electrical response with a conspicuous outward component. This current was generated through P2Y 2 receptor activation and opening of K + channels, K Ca 3.1, as indicated by electrophysiological and pharmacological analysis, as well as by immunodetection and specific silencing of P2Y 2 or K Ca 3.1 gene by esiRNA transfection. Low µM ATP concentration increased SKOV-3 cell migration, which was strongly inhibited by K Ca 3.1 channel blockers and by esiRNA-generated P2Y 2 or K Ca 3.1 downregulation. Finally, in human ovarian tumors, the P2Y 2 and K Ca 3.1 proteins are expressed and co-localized in neoplastic cells. Thus, stimulation of P2Y 2 receptors expressed in SKOV-3 cells promotes motility through K Ca 3.1 activation. Since P2Y 2 and K Ca 3.1 are co-expressed in primary tumors, our findings suggest that they may play a role in cancer progression.