EAG2 potassium channel with evolutionarily conserved function as a brain tumor target

Xi Huang, Ye He, Adrian M. Dubuc, Rintaro Hashizume, Wei Zhang, Jüri Reimand, Huanghe Yang, Tongfei A. Wang, Samantha J. Stehbens, Susan Younger, Suzanne Barshow, Sijun Zhu, Michael K. Cooper, John Peacock, Vijay Ramaswamy, Livia Garzia, Xiaochong Wu, Marc Remke, Craig M. Forester, Charles C. KimWilliam A. Weiss, C. David James, Marc A. Shuman, Gary D. Bader, Sabine Mueller, Michael D. Taylor, Yuh Nung Jan*, Lily Yeh Jan

*Corresponding author for this work

Research output: Contribution to journalArticle

27 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1236-1246
Number of pages11
JournalNature Neuroscience
Volume18
Issue number9
DOIs
StatePublished - Aug 26 2015

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ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Huang, X., He, Y., Dubuc, A. M., Hashizume, R., Zhang, W., Reimand, J., Yang, H., Wang, T. A., Stehbens, S. J., Younger, S., Barshow, S., Zhu, S., Cooper, M. K., Peacock, J., Ramaswamy, V., Garzia, L., Wu, X., Remke, M., Forester, C. M., ... Jan, L. Y. (2015). EAG2 potassium channel with evolutionarily conserved function as a brain tumor target. Nature Neuroscience, 18(9), 1236-1246. https://doi.org/10.1038/nn.4088