Knockdown of EphB1 receptor decreases medulloblastoma cell growth and migration and increases cellular radiosensitization

The expression of members of the Eph family of receptor tyrosine kinases and their ephrin ligands is frequently dysregulated in medulloblastomas. We assessed the expression and functional role of EphB1 in medulloblastoma cell lines and engineered mouse models. mRNA and protein expression profiling s...

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Main Authors:	Bhatia, Shilpa, Baig, Nimrah A., Timofeeva, Olga, Pasquale, Elena B., Hirsch, Kellen, MacDonald, Tobey J., Dritschilo, Anatoly, Lee, Yi Chien, Henkemeyer, Mark, Rood, Brian, Jung, Mira, Wang, Xiao-Jing, Kool, Marcel, Rodriguez, Olga, Albanese, Chris, Karam, Sana D.
Format:	Online
Language:	English
Published:	Impact Journals LLC 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496193/

id	pubmed-4496193
recordtype	oai_dc
spelling	pubmed-44961932015-07-10 Knockdown of EphB1 receptor decreases medulloblastoma cell growth and migration and increases cellular radiosensitization Bhatia, Shilpa Baig, Nimrah A. Timofeeva, Olga Pasquale, Elena B. Hirsch, Kellen MacDonald, Tobey J. Dritschilo, Anatoly Lee, Yi Chien Henkemeyer, Mark Rood, Brian Jung, Mira Wang, Xiao-Jing Kool, Marcel Rodriguez, Olga Albanese, Chris Karam, Sana D. Research Paper The expression of members of the Eph family of receptor tyrosine kinases and their ephrin ligands is frequently dysregulated in medulloblastomas. We assessed the expression and functional role of EphB1 in medulloblastoma cell lines and engineered mouse models. mRNA and protein expression profiling showed expression of EphB1 receptor in the human medulloblastoma cell lines DAOY and UW228. EphB1 downregulation reduced cell growth and viability, decreased the expression of important cell cycle regulators, and increased the percentage of cells in G1 phase of the cell cycle. It also modulated the expression of proliferation, and cell survival markers. In addition, EphB1 knockdown in DAOY cells resulted in significant decrease in migration, which correlated with decreased β1-integrin expression and levels of phosphorylated Src. Furthermore, EphB1 knockdown enhanced cellular radiosensitization of medulloblastoma cells in culture and in a genetically engineered mouse medulloblastoma model. Using genetically engineered mouse models, we established that genetic loss of EphB1 resulted in a significant delay in tumor recurrence following irradiation compared to EphB1-expressing control tumors. Taken together, our findings establish that EphB1 plays a key role in medulloblastoma cell growth, viability, migration, and radiation sensitivity, making EphB1 a promising therapeutic target. Impact Journals LLC 2015-03-30 /pmc/articles/PMC4496193/ /pubmed/25879388 Text en Copyright: © 2015 Bhatia et al. http://creativecommons.org/licenses/by/2.5/ 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 credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Bhatia, Shilpa Baig, Nimrah A. Timofeeva, Olga Pasquale, Elena B. Hirsch, Kellen MacDonald, Tobey J. Dritschilo, Anatoly Lee, Yi Chien Henkemeyer, Mark Rood, Brian Jung, Mira Wang, Xiao-Jing Kool, Marcel Rodriguez, Olga Albanese, Chris Karam, Sana D.
spellingShingle	Bhatia, Shilpa Baig, Nimrah A. Timofeeva, Olga Pasquale, Elena B. Hirsch, Kellen MacDonald, Tobey J. Dritschilo, Anatoly Lee, Yi Chien Henkemeyer, Mark Rood, Brian Jung, Mira Wang, Xiao-Jing Kool, Marcel Rodriguez, Olga Albanese, Chris Karam, Sana D. Knockdown of EphB1 receptor decreases medulloblastoma cell growth and migration and increases cellular radiosensitization
author_facet	Bhatia, Shilpa Baig, Nimrah A. Timofeeva, Olga Pasquale, Elena B. Hirsch, Kellen MacDonald, Tobey J. Dritschilo, Anatoly Lee, Yi Chien Henkemeyer, Mark Rood, Brian Jung, Mira Wang, Xiao-Jing Kool, Marcel Rodriguez, Olga Albanese, Chris Karam, Sana D.
author_sort	Bhatia, Shilpa
title	Knockdown of EphB1 receptor decreases medulloblastoma cell growth and migration and increases cellular radiosensitization
title_short	Knockdown of EphB1 receptor decreases medulloblastoma cell growth and migration and increases cellular radiosensitization
title_full	Knockdown of EphB1 receptor decreases medulloblastoma cell growth and migration and increases cellular radiosensitization
title_fullStr	Knockdown of EphB1 receptor decreases medulloblastoma cell growth and migration and increases cellular radiosensitization
title_full_unstemmed	Knockdown of EphB1 receptor decreases medulloblastoma cell growth and migration and increases cellular radiosensitization
title_sort	knockdown of ephb1 receptor decreases medulloblastoma cell growth and migration and increases cellular radiosensitization
description	The expression of members of the Eph family of receptor tyrosine kinases and their ephrin ligands is frequently dysregulated in medulloblastomas. We assessed the expression and functional role of EphB1 in medulloblastoma cell lines and engineered mouse models. mRNA and protein expression profiling showed expression of EphB1 receptor in the human medulloblastoma cell lines DAOY and UW228. EphB1 downregulation reduced cell growth and viability, decreased the expression of important cell cycle regulators, and increased the percentage of cells in G1 phase of the cell cycle. It also modulated the expression of proliferation, and cell survival markers. In addition, EphB1 knockdown in DAOY cells resulted in significant decrease in migration, which correlated with decreased β1-integrin expression and levels of phosphorylated Src. Furthermore, EphB1 knockdown enhanced cellular radiosensitization of medulloblastoma cells in culture and in a genetically engineered mouse medulloblastoma model. Using genetically engineered mouse models, we established that genetic loss of EphB1 resulted in a significant delay in tumor recurrence following irradiation compared to EphB1-expressing control tumors. Taken together, our findings establish that EphB1 plays a key role in medulloblastoma cell growth, viability, migration, and radiation sensitivity, making EphB1 a promising therapeutic target.
publisher	Impact Journals LLC
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496193/
_version_	1613245793413627904

Knockdown of EphB1 receptor decreases medulloblastoma cell growth and migration and increases cellular radiosensitization

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