Cord blood stem cells inhibit epidermal growth factor receptor translocation to mitochondria in glioblastoma.

<h4>Background</h4>Overexpression of EGFR is one of the most frequently diagnosed genetic aberrations of glioblastoma multiforme (GBM). EGFR signaling is involved in diverse cellular functions and is dependent on the type of preferred receptor complexes. EGFR translocation to mitochondri...

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Autores principales:	Venkata Ramesh Dasari, Kiran Kumar Velpula, Kiranmai Alapati, Meena Gujrati, Andrew J Tsung
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a208bdda37754326a7b62c5c9c710b41
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spelling	oai:doaj.org-article:a208bdda37754326a7b62c5c9c710b412021-11-18T07:28:18ZCord blood stem cells inhibit epidermal growth factor receptor translocation to mitochondria in glioblastoma.1932-620310.1371/journal.pone.0031884https://doaj.org/article/a208bdda37754326a7b62c5c9c710b412012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22348136/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Overexpression of EGFR is one of the most frequently diagnosed genetic aberrations of glioblastoma multiforme (GBM). EGFR signaling is involved in diverse cellular functions and is dependent on the type of preferred receptor complexes. EGFR translocation to mitochondria has been reported recently in different cancer types. However, mechanistic aspects of EGFR translocation to mitochondria in GBM have not been evaluated to date.<h4>Methodology/principle findings</h4>In the present study, we analyzed the expression of EGFR in GBM-patient derived specimens using immunohistochemistry, reverse-transcription based PCR and Western blotting techniques. In clinical samples, EGFR co-localizes with FAK in mitochondria. We evaluated this previous observation in standard glioma cell lines and in vivo mice xenografts. We further analyzed the effect of human umbilical cord blood stem cells (hUCBSC) on the inhibition of EGFR expression and EGFR signaling in glioma cells and xenografts. Treatment with hUCBSC inhibited the expression of EGFR and its co-localization with FAK in glioma cells. Also, hUCBSC inhibited the co-localization of activated forms of EGFR, FAK and c-Src in mitochondria of glioma cells and xenografts. In addition, hUCBSC also inhibited EGFR signaling proteins in glioma cells both in vitro and in vivo.<h4>Conclusions/significance</h4>We have shown that hUCBSC treatments inhibit phosphorylation of EGFR, FAK and c-Src forms. Our findings associate EGFR expression and its localization to mitochondria with specific biological functions in GBM cells and provide relevant preclinical information that can be used for the development of effective hUCBSC-based therapies.Venkata Ramesh DasariKiran Kumar VelpulaKiranmai AlapatiMeena GujratiAndrew J TsungPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 2, p e31884 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Venkata Ramesh Dasari Kiran Kumar Velpula Kiranmai Alapati Meena Gujrati Andrew J Tsung Cord blood stem cells inhibit epidermal growth factor receptor translocation to mitochondria in glioblastoma.
description	<h4>Background</h4>Overexpression of EGFR is one of the most frequently diagnosed genetic aberrations of glioblastoma multiforme (GBM). EGFR signaling is involved in diverse cellular functions and is dependent on the type of preferred receptor complexes. EGFR translocation to mitochondria has been reported recently in different cancer types. However, mechanistic aspects of EGFR translocation to mitochondria in GBM have not been evaluated to date.<h4>Methodology/principle findings</h4>In the present study, we analyzed the expression of EGFR in GBM-patient derived specimens using immunohistochemistry, reverse-transcription based PCR and Western blotting techniques. In clinical samples, EGFR co-localizes with FAK in mitochondria. We evaluated this previous observation in standard glioma cell lines and in vivo mice xenografts. We further analyzed the effect of human umbilical cord blood stem cells (hUCBSC) on the inhibition of EGFR expression and EGFR signaling in glioma cells and xenografts. Treatment with hUCBSC inhibited the expression of EGFR and its co-localization with FAK in glioma cells. Also, hUCBSC inhibited the co-localization of activated forms of EGFR, FAK and c-Src in mitochondria of glioma cells and xenografts. In addition, hUCBSC also inhibited EGFR signaling proteins in glioma cells both in vitro and in vivo.<h4>Conclusions/significance</h4>We have shown that hUCBSC treatments inhibit phosphorylation of EGFR, FAK and c-Src forms. Our findings associate EGFR expression and its localization to mitochondria with specific biological functions in GBM cells and provide relevant preclinical information that can be used for the development of effective hUCBSC-based therapies.
format	article
author	Venkata Ramesh Dasari Kiran Kumar Velpula Kiranmai Alapati Meena Gujrati Andrew J Tsung
author_facet	Venkata Ramesh Dasari Kiran Kumar Velpula Kiranmai Alapati Meena Gujrati Andrew J Tsung
author_sort	Venkata Ramesh Dasari
title	Cord blood stem cells inhibit epidermal growth factor receptor translocation to mitochondria in glioblastoma.
title_short	Cord blood stem cells inhibit epidermal growth factor receptor translocation to mitochondria in glioblastoma.
title_full	Cord blood stem cells inhibit epidermal growth factor receptor translocation to mitochondria in glioblastoma.
title_fullStr	Cord blood stem cells inhibit epidermal growth factor receptor translocation to mitochondria in glioblastoma.
title_full_unstemmed	Cord blood stem cells inhibit epidermal growth factor receptor translocation to mitochondria in glioblastoma.
title_sort	cord blood stem cells inhibit epidermal growth factor receptor translocation to mitochondria in glioblastoma.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/a208bdda37754326a7b62c5c9c710b41
work_keys_str_mv	AT venkatarameshdasari cordbloodstemcellsinhibitepidermalgrowthfactorreceptortranslocationtomitochondriainglioblastoma AT kirankumarvelpula cordbloodstemcellsinhibitepidermalgrowthfactorreceptortranslocationtomitochondriainglioblastoma AT kiranmaialapati cordbloodstemcellsinhibitepidermalgrowthfactorreceptortranslocationtomitochondriainglioblastoma AT meenagujrati cordbloodstemcellsinhibitepidermalgrowthfactorreceptortranslocationtomitochondriainglioblastoma AT andrewjtsung cordbloodstemcellsinhibitepidermalgrowthfactorreceptortranslocationtomitochondriainglioblastoma
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Cord blood stem cells inhibit epidermal growth factor receptor translocation to mitochondria in glioblastoma.

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