Abstract 1950: Targeted silencing of NaV1.5 channel suppresses cell proliferation and invasion in ovarian cancer cells through inhibition of PI3K/AKT and Integrinβ-1/FAK/Src axis
Authors: Mumin Alper Erdogan, Bulent Ozpolat
Journal: Cancer Research (2018)

Abstract Ovarian cancer (OCa) is the leading cause of gynecological cancer related deaths. OCa is one of the most aggressive cancer and associated with poor prognosis and survival rates (5-year survival rates about 50%). OCa cells have highly invasive metastatic phenotype due to mutations, altered signaling pathways and deregulated of control mechanisms and patients with metastatic disease have poorer prognosis (5-year survival is 20%). The major reasons for patient death include significant intratumoral heterogeneity, early metastasis and development of resistance to currently used chemotherapeutics. Therefore, identification of novel molecular targets and therapeutics strategies are urgently needed to enhance the efficacy of current therapies and prolong patient survival. Ion channels are important signaling molecules expressed in a wide range of tissues where they have significant involvement in determining a variety of cellular functions: solute transport, volume control, enzyme activity, secretion, invasion, gene expression, excitation-contraction coupling and intercellular communication. Studies indicated that there are significant differences in the regulation and the function of ion channels between normal and cancer cells. Voltage gated sodium channels (VGSC) is a group of ion channels that has been correlated with OCa because of their higher expression in highly metastatic ovarian cancer cells. Importantly, VGSC activity contributes to many cellular behaviors integral to metastasis in breast and other cancers including OCA. In this study, we investigated the NaV1.5 as integral component of the metastatic process in human OCa. The aim of the current study was to reveal molecular mechanisms underlying the effects of NaV1.5 down-regulation and investigate the effects on OCa in vitro. In this study, the ovarian cancer cell lines (HEYA8, SKOV3-IP1, SKOV3-TR (taxol resistant)) were used. NaV1.5 and Control non-silencing small interfering RNAs (siRNA) were employed for therapy. As in vitro experiments, cell proliferation, colony formation, invasion, western blot analysis were performed. Our results showed that specific NaV1.5 siRNA treatments caused a significant reduction in cell proliferation, colony formation, and invasion capacity in OCa cells (p&amp;lt;0.0001). To reveal molecular mechanisms underlying the effects of NaV1.5 down-regulation, we evaluated signaling pathways regulating cell proliferation and invasion/metastasis by western blot analysis and found that NaV1.5 expression promotes expression of PI3K/AKT, Integrinβ1/FAK/Src and P70S6K. In conclusion, our results suggest that Nav1.5 channels may contribute OCa tumorigenesis and metastasis through the upregulation of oncogenic pathways and serve as a potential therapeutic target in OCa. Citation Format: Mumin Alper Erdogan, Bulent Ozpolat. Targeted silencing of NaV1.5 channel suppresses cell proliferation and invasion in ovarian cancer cells through inhibition of PI3K/AKT and Integrinβ-1/FAK/Src axis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1950.