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Serine/Threonine Kinase 17A Is a Novel Candidate for Therapeutic Targeting in Glioblastoma

STK17A is a relatively uncharacterized member of the death-associated protein family of serine/threonine kinases which have previously been associated with cell death and apoptosis. Our prior work established that STK17A is a novel p53 target gene that is induced by a variety of DNA damaging agents...

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Autores principales: Mao, Pingping, Hever-Jardine, Mary P., Rahme, Gilbert J., Yang, Eric, Tam, Janice, Kodali, Anita, Biswal, Bijesh, Fadul, Camilo E., Gaur, Arti, Israel, Mark A., Spinella, Michael J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3842963/
https://www.ncbi.nlm.nih.gov/pubmed/24312360
http://dx.doi.org/10.1371/journal.pone.0081803
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author Mao, Pingping
Hever-Jardine, Mary P.
Rahme, Gilbert J.
Yang, Eric
Tam, Janice
Kodali, Anita
Biswal, Bijesh
Fadul, Camilo E.
Gaur, Arti
Israel, Mark A.
Spinella, Michael J.
author_facet Mao, Pingping
Hever-Jardine, Mary P.
Rahme, Gilbert J.
Yang, Eric
Tam, Janice
Kodali, Anita
Biswal, Bijesh
Fadul, Camilo E.
Gaur, Arti
Israel, Mark A.
Spinella, Michael J.
author_sort Mao, Pingping
collection PubMed
description STK17A is a relatively uncharacterized member of the death-associated protein family of serine/threonine kinases which have previously been associated with cell death and apoptosis. Our prior work established that STK17A is a novel p53 target gene that is induced by a variety of DNA damaging agents in a p53-dependent manner. In this study we have uncovered an additional, unanticipated role for STK17A as a candidate promoter of cell proliferation and survival in glioblastoma (GBM). Unexpectedly, it was found that STK17A is highly overexpressed in a grade-dependent manner in gliomas compared to normal brain and other cancer cell types with the highest level of expression in GBM. Knockdown of STK17A in GBM cells results in a dramatic alteration in cell shape that is associated with decreased proliferation, clonogenicity, migration, invasion and anchorage independent colony formation. STK17A knockdown also sensitizes GBM cells to genotoxic stress. STK17A overexpression is associated with a significant survival disadvantage among patients with glioma which is independent of age, molecular phenotype, IDH1 mutation, PTEN loss, and alterations in the p53 pathway and partially independent of grade. In summary, we demonstrate that STK17A provides a proliferative and survival advantage to GBM cells and is a potential target to be exploited therapeutically in patients with glioma.
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spelling pubmed-38429632013-12-05 Serine/Threonine Kinase 17A Is a Novel Candidate for Therapeutic Targeting in Glioblastoma Mao, Pingping Hever-Jardine, Mary P. Rahme, Gilbert J. Yang, Eric Tam, Janice Kodali, Anita Biswal, Bijesh Fadul, Camilo E. Gaur, Arti Israel, Mark A. Spinella, Michael J. PLoS One Research Article STK17A is a relatively uncharacterized member of the death-associated protein family of serine/threonine kinases which have previously been associated with cell death and apoptosis. Our prior work established that STK17A is a novel p53 target gene that is induced by a variety of DNA damaging agents in a p53-dependent manner. In this study we have uncovered an additional, unanticipated role for STK17A as a candidate promoter of cell proliferation and survival in glioblastoma (GBM). Unexpectedly, it was found that STK17A is highly overexpressed in a grade-dependent manner in gliomas compared to normal brain and other cancer cell types with the highest level of expression in GBM. Knockdown of STK17A in GBM cells results in a dramatic alteration in cell shape that is associated with decreased proliferation, clonogenicity, migration, invasion and anchorage independent colony formation. STK17A knockdown also sensitizes GBM cells to genotoxic stress. STK17A overexpression is associated with a significant survival disadvantage among patients with glioma which is independent of age, molecular phenotype, IDH1 mutation, PTEN loss, and alterations in the p53 pathway and partially independent of grade. In summary, we demonstrate that STK17A provides a proliferative and survival advantage to GBM cells and is a potential target to be exploited therapeutically in patients with glioma. Public Library of Science 2013-11-28 /pmc/articles/PMC3842963/ /pubmed/24312360 http://dx.doi.org/10.1371/journal.pone.0081803 Text en © 2013 Mao 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Mao, Pingping
Hever-Jardine, Mary P.
Rahme, Gilbert J.
Yang, Eric
Tam, Janice
Kodali, Anita
Biswal, Bijesh
Fadul, Camilo E.
Gaur, Arti
Israel, Mark A.
Spinella, Michael J.
Serine/Threonine Kinase 17A Is a Novel Candidate for Therapeutic Targeting in Glioblastoma
title Serine/Threonine Kinase 17A Is a Novel Candidate for Therapeutic Targeting in Glioblastoma
title_full Serine/Threonine Kinase 17A Is a Novel Candidate for Therapeutic Targeting in Glioblastoma
title_fullStr Serine/Threonine Kinase 17A Is a Novel Candidate for Therapeutic Targeting in Glioblastoma
title_full_unstemmed Serine/Threonine Kinase 17A Is a Novel Candidate for Therapeutic Targeting in Glioblastoma
title_short Serine/Threonine Kinase 17A Is a Novel Candidate for Therapeutic Targeting in Glioblastoma
title_sort serine/threonine kinase 17a is a novel candidate for therapeutic targeting in glioblastoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3842963/
https://www.ncbi.nlm.nih.gov/pubmed/24312360
http://dx.doi.org/10.1371/journal.pone.0081803
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