EAG2 potassium channel with evolutionarily conserved function as a brain tumor target.
Journal Article (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
- PMC4639927
Electronic International Standard Serial Number (EISSN)
- 1546-1726
Digital Object Identifier (DOI)
- 10.1038/nn.4088
Language
- eng
Conference Location
- United States