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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Huang, X; He, Y; Dubuc, AM; Hashizume, R; Zhang, W; Reimand, J; Yang, H; Wang, TA; Stehbens, SJ; Younger, S; Barshow, S; Zhu, S; Cooper, MK; Peacock, J; Ramaswamy, V; Garzia, L; Wu, X; Remke, M; Forester, CM; Kim, CC; Weiss, WA; James, CD; Shuman, MA; Bader, GD; Mueller, S; Taylor, MD; Jan, YN; Jan, LY

Published Date

  • September 2015

Published In

Volume / Issue

  • 18 / 9

Start / End Page

  • 1236 - 1246

PubMed ID

  • 26258683

Pubmed Central ID

  • 26258683

Electronic International Standard Serial Number (EISSN)

  • 1546-1726

International Standard Serial Number (ISSN)

  • 1097-6256

Digital Object Identifier (DOI)

  • 10.1038/nn.4088

Language

  • eng