| Literature DB >> 26258683 |
Xi Huang1,2, Ye He1,2, Adrian M Dubuc3, Rintaro Hashizume4, Wei Zhang1,2, Jüri Reimand5, Huanghe Yang1,2, Tongfei A Wang1,2, Samantha J Stehbens6, Susan Younger1,2, Suzanne Barshow1,2, Sijun Zhu1,2, Michael K Cooper7, John Peacock3, Vijay Ramaswamy3, Livia Garzia3, Xiaochong Wu3, Marc Remke3, Craig M Forester8, Charles C Kim9, William A Weiss8,10,11, C David James4, Marc A Shuman12, Gary D Bader5, Sabine Mueller11, Michael D Taylor3, Yuh Nung Jan1,2, Lily Yeh Jan1,2.
Abstract
Over 20% of the drugs for treating human diseases target ion channels, but no cancer drug approved by the US Food and Drug Administration (FDA) is intended to target an ion channel. We found that the EAG2 (Ether-a-go-go 2) potassium channel has an evolutionarily conserved function for promoting brain tumor growth and metastasis, delineate downstream pathways, and uncover a mechanism for different potassium channels to functionally cooperate and regulate mitotic cell volume and tumor progression. EAG2 potassium channel was enriched at the trailing edge of migrating medulloblastoma (MB) cells to regulate local cell volume dynamics, thereby facilitating cell motility. We identified the FDA-approved antipsychotic drug thioridazine as an EAG2 channel blocker that reduces xenografted MB growth and metastasis, and present a case report of repurposing thioridazine for treating a human patient. Our findings illustrate the potential of targeting ion channels in cancer treatment.Entities:
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Year: 2015 PMID： 26258683 PMCID： PMC4639927 DOI： 10.1038/nn.4088
Source DB: PubMed Journal: Nat Neurosci ISSN： 1097-6256 Impact factor: 24.884