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Potassium channel-driven bioelectric signaling affects the metastatic potential of triple negative breast cancer

ABSTRACT: Our data demonstrate that altering the RMP of triple-negative breast cancer (TNBC) cells by manipulating potassium channels increases in vitro invasion, tumor growth, and metastasis, inducing changes in gene expression associated with cell adhesion. We describe a novel mechanism for RMP-mediated cell migration involving cadherin-11 and the MAPK pathway. Importantly, we identify a new treatment strategy for metastatic TNBC by repurposing FDA-approved potassium channel blockers. Our results provide an understanding of a mechanism by which the bioelectricity regulates cancer cell invasion and metastasis that can advance the development of a potential new class of TNBC therapeutics.

ORGANISM(S): Homo sapiens

PROVIDER: GSE171150 | GEO | 2021/09/01

REPOSITORIES: GEO

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

Project description:Characterizing the impact of pharmacological and shRNA-mediated silencing of EAG2 in medulloblastoma. Medulloblastoma (MB) is the most common pediatric CNS malignancy. Previously, we demonstrated that overexpression of the ion channel EAG2, identified in a subset of histological and molecular subtypes of this disease, functionally contributes to tumor progression (PMID: 22855790). Here, we demonstrate the evolutionarily conserved function of EAG2 potassium channel in promoting brain tumor growth and metastasis, delineate downstream pathways and uncover a co-option mechanism for different potassium channels to regulate mitotic cell volume and tumor progression. We show that EAG2 potassium channel is enriched at the trailing edge of migrating MB cells to regulate local cell volume dynamics, thereby facilitating cell motility. We identify 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 thus illustrate the potential of targeting ion channels in cancer treatment.

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A forward genetic screen identifies potassium channel essentiality in SHH medulloblastoma maintenance [RNA-seq]

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