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

AI Article Synopsis

  • * The EAG2 channel helps regulate cell volume and motility in medulloblastoma cells, promoting tumor progression through conserved evolutionary functions.
  • * Thioridazine, an FDA-approved antipsychotic, is discovered to block EAG2, reducing tumor growth and metastasis, showing promise for repurposing in cancer treatment.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4639927PMC
http://dx.doi.org/10.1038/nn.4088DOI Listing

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