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

Publication ,  Journal Article
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 ...
Published in: Nat Neurosci
September 2015

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.

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Published In

Nat Neurosci

DOI

EISSN

1546-1726

Publication Date

September 2015

Volume

18

Issue

9

Start / End Page

1236 / 1246

Location

United States

Related Subject Headings

  • Young Adult
  • Xenograft Model Antitumor Assays
  • Tumor Cells, Cultured
  • Thioridazine
  • Neurology & Neurosurgery
  • Mice, Transgenic
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Huang, X., He, Y., Dubuc, A. M., Hashizume, R., Zhang, W., Reimand, J., … Jan, L. Y. (2015). EAG2 potassium channel with evolutionarily conserved function as a brain tumor target. Nat Neurosci, 18(9), 1236–1246. https://doi.org/10.1038/nn.4088
Huang, Xi, Ye He, Adrian M. Dubuc, Rintaro Hashizume, Wei Zhang, Jüri Reimand, Huanghe Yang, et al. “EAG2 potassium channel with evolutionarily conserved function as a brain tumor target.Nat Neurosci 18, no. 9 (September 2015): 1236–46. https://doi.org/10.1038/nn.4088.
Huang X, He Y, Dubuc AM, Hashizume R, Zhang W, Reimand J, et al. EAG2 potassium channel with evolutionarily conserved function as a brain tumor target. Nat Neurosci. 2015 Sep;18(9):1236–46.
Huang, Xi, et al. “EAG2 potassium channel with evolutionarily conserved function as a brain tumor target.Nat Neurosci, vol. 18, no. 9, Sept. 2015, pp. 1236–46. Pubmed, doi:10.1038/nn.4088.
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. EAG2 potassium channel with evolutionarily conserved function as a brain tumor target. Nat Neurosci. 2015 Sep;18(9):1236–1246.

Published In

Nat Neurosci

DOI

EISSN

1546-1726

Publication Date

September 2015

Volume

18

Issue

9

Start / End Page

1236 / 1246

Location

United States

Related Subject Headings

  • Young Adult
  • Xenograft Model Antitumor Assays
  • Tumor Cells, Cultured
  • Thioridazine
  • Neurology & Neurosurgery
  • Mice, Transgenic
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Male