K_ca3.1 Activation Via P2y₂ Purinergic Receptors Promotes Human Ovarian Cancer Cell (Skov-3) Migration

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 Ca²⁺ concentration ([Ca²⁺]_i) and, concurrently, it evoked a complex electrical response with a conspicuous outward component. This current was generated through P2Y₂ receptor activation and opening of K⁺ channels, K_Ca3.1, as indicated by electrophysiological and pharmacological analysis, as well as by immunodetection and specific silencing of P2Y₂ or K_Ca3.1 gene by esiRNA transfection. Low µM ATP concentration increased SKOV-3 cell migration, which was strongly inhibited by K_Ca3.1 channel blockers and by esiRNA-generated P2Y₂ or K_Ca3.1 downregulation. Finally, in human ovarian tumors, the P2Y₂ and K_Ca3.1 proteins are expressed and co-localized in neoplastic cells. Thus, stimulation of P2Y₂ receptors expressed in SKOV-3 cells promotes motility through K_Ca3.1 activation. Since P2Y₂ and K_Ca3.1 are co-expressed in primary tumors, our findings suggest that they may play a role in cancer progression.