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Ion channel expression patterns in glioblastoma stem cells with functional and therapeutic implications for malignancy

Ion channels and transporters have increasingly recognized roles in cancer progression through the regulation of cell proliferation, migration, and death. Glioblastoma stem-like cells (GSCs) are a source of tumor formation and recurrence in glioblastoma multiforme, a highly aggressive brain cancer,...

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Autores principales: Pollak, Julia, Rai, Karan G., Funk, Cory C., Arora, Sonali, Lee, Eunjee, Zhu, Jun, Price, Nathan D., Paddison, Patrick J., Ramirez, Jan-Marino, Rostomily, Robert C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338779/
https://www.ncbi.nlm.nih.gov/pubmed/28264064
http://dx.doi.org/10.1371/journal.pone.0172884
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author Pollak, Julia
Rai, Karan G.
Funk, Cory C.
Arora, Sonali
Lee, Eunjee
Zhu, Jun
Price, Nathan D.
Paddison, Patrick J.
Ramirez, Jan-Marino
Rostomily, Robert C.
author_facet Pollak, Julia
Rai, Karan G.
Funk, Cory C.
Arora, Sonali
Lee, Eunjee
Zhu, Jun
Price, Nathan D.
Paddison, Patrick J.
Ramirez, Jan-Marino
Rostomily, Robert C.
author_sort Pollak, Julia
collection PubMed
description Ion channels and transporters have increasingly recognized roles in cancer progression through the regulation of cell proliferation, migration, and death. Glioblastoma stem-like cells (GSCs) are a source of tumor formation and recurrence in glioblastoma multiforme, a highly aggressive brain cancer, suggesting that ion channel expression may be perturbed in this population. However, little is known about the expression and functional relevance of ion channels that may contribute to GSC malignancy. Using RNA sequencing, we assessed the enrichment of ion channels in GSC isolates and non-tumor neural cell types. We identified a unique set of GSC-enriched ion channels using differential expression analysis that is also associated with distinct gene mutation signatures. In support of potential clinical relevance, expression of selected GSC-enriched ion channels evaluated in human glioblastoma databases of The Cancer Genome Atlas and Ivy Glioblastoma Atlas Project correlated with patient survival times. Finally, genetic knockdown as well as pharmacological inhibition of individual or classes of GSC-enriched ion channels constrained growth of GSCs compared to normal neural stem cells. This first-in-kind global examination characterizes ion channels enriched in GSCs and explores their potential clinical relevance to glioblastoma molecular subtypes, gene mutations, survival outcomes, regional tumor expression, and experimental responses to loss-of-function. Together, the data support the potential biological and therapeutic impact of ion channels on GSC malignancy and provide strong rationale for further examination of their mechanistic and therapeutic importance.
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spelling pubmed-53387792017-03-10 Ion channel expression patterns in glioblastoma stem cells with functional and therapeutic implications for malignancy Pollak, Julia Rai, Karan G. Funk, Cory C. Arora, Sonali Lee, Eunjee Zhu, Jun Price, Nathan D. Paddison, Patrick J. Ramirez, Jan-Marino Rostomily, Robert C. PLoS One Research Article Ion channels and transporters have increasingly recognized roles in cancer progression through the regulation of cell proliferation, migration, and death. Glioblastoma stem-like cells (GSCs) are a source of tumor formation and recurrence in glioblastoma multiforme, a highly aggressive brain cancer, suggesting that ion channel expression may be perturbed in this population. However, little is known about the expression and functional relevance of ion channels that may contribute to GSC malignancy. Using RNA sequencing, we assessed the enrichment of ion channels in GSC isolates and non-tumor neural cell types. We identified a unique set of GSC-enriched ion channels using differential expression analysis that is also associated with distinct gene mutation signatures. In support of potential clinical relevance, expression of selected GSC-enriched ion channels evaluated in human glioblastoma databases of The Cancer Genome Atlas and Ivy Glioblastoma Atlas Project correlated with patient survival times. Finally, genetic knockdown as well as pharmacological inhibition of individual or classes of GSC-enriched ion channels constrained growth of GSCs compared to normal neural stem cells. This first-in-kind global examination characterizes ion channels enriched in GSCs and explores their potential clinical relevance to glioblastoma molecular subtypes, gene mutations, survival outcomes, regional tumor expression, and experimental responses to loss-of-function. Together, the data support the potential biological and therapeutic impact of ion channels on GSC malignancy and provide strong rationale for further examination of their mechanistic and therapeutic importance. Public Library of Science 2017-03-06 /pmc/articles/PMC5338779/ /pubmed/28264064 http://dx.doi.org/10.1371/journal.pone.0172884 Text en © 2017 Pollak et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Pollak, Julia
Rai, Karan G.
Funk, Cory C.
Arora, Sonali
Lee, Eunjee
Zhu, Jun
Price, Nathan D.
Paddison, Patrick J.
Ramirez, Jan-Marino
Rostomily, Robert C.
Ion channel expression patterns in glioblastoma stem cells with functional and therapeutic implications for malignancy
title Ion channel expression patterns in glioblastoma stem cells with functional and therapeutic implications for malignancy
title_full Ion channel expression patterns in glioblastoma stem cells with functional and therapeutic implications for malignancy
title_fullStr Ion channel expression patterns in glioblastoma stem cells with functional and therapeutic implications for malignancy
title_full_unstemmed Ion channel expression patterns in glioblastoma stem cells with functional and therapeutic implications for malignancy
title_short Ion channel expression patterns in glioblastoma stem cells with functional and therapeutic implications for malignancy
title_sort ion channel expression patterns in glioblastoma stem cells with functional and therapeutic implications for malignancy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338779/
https://www.ncbi.nlm.nih.gov/pubmed/28264064
http://dx.doi.org/10.1371/journal.pone.0172884
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