LC3A Silencing Hinders Aggresome Vimentin Cage Clearance in Primary Choroid Plexus Carcinoma

Abstract Aggresomes are transient microtubule-dependent inclusion bodies that sequester misfolded proteins and are ultimately removed by autophagy. Here we report the generation of a choroid plexus carcinoma cell line; Children’s Cancer Hospital Egypt (CCHE)-45, which is characterized by the constit...

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Autores principales:	Marwa Nassar, Heba Samaha, Myret Ghabriel, Maha Yehia, Hala Taha, Sherin Salem, Khaled Shaaban, Mariam Omar, Nabil Ahmed, Shahenda El-Naggar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b83392284343455b92814c88aef8b78b
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spelling	oai:doaj.org-article:b83392284343455b92814c88aef8b78b2021-12-02T11:52:21ZLC3A Silencing Hinders Aggresome Vimentin Cage Clearance in Primary Choroid Plexus Carcinoma10.1038/s41598-017-07403-52045-2322https://doaj.org/article/b83392284343455b92814c88aef8b78b2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07403-5https://doaj.org/toc/2045-2322Abstract Aggresomes are transient microtubule-dependent inclusion bodies that sequester misfolded proteins and are ultimately removed by autophagy. Here we report the generation of a choroid plexus carcinoma cell line; Children’s Cancer Hospital Egypt (CCHE)-45, which is characterized by the constitutive formation of aggresomes. When examining the autophagy pathway as the main route for aggresomes clearance, CCHE-45 cells displayed increased autophagy flux mediated by MAP1LC3B. MAP1LC3A-Variant1 gene expression was silenced by promoter methylation. Restoring MAP1LC3A-Variant1 expression resulted in the formation of MAP1LC3A positive autophagosmes and the disruption of the aggresomes' vimentin cage independent of MAP1LC3B positive autophagosomes. Our data supports the notion that basal quality control autophagy and vimentin cage clearance in CCHE-45 are mediated by MAP1LC3A. Hence we propose that absence of MAP1LC3A disrupts the autophagic pathway and leads to the failure of aggresome vimentin cage degradation. Consequently, this could represent a targetable pathway in autophagy-dependent cancers.Marwa NassarHeba SamahaMyret GhabrielMaha YehiaHala TahaSherin SalemKhaled ShaabanMariam OmarNabil AhmedShahenda El-NaggarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marwa Nassar Heba Samaha Myret Ghabriel Maha Yehia Hala Taha Sherin Salem Khaled Shaaban Mariam Omar Nabil Ahmed Shahenda El-Naggar LC3A Silencing Hinders Aggresome Vimentin Cage Clearance in Primary Choroid Plexus Carcinoma
description	Abstract Aggresomes are transient microtubule-dependent inclusion bodies that sequester misfolded proteins and are ultimately removed by autophagy. Here we report the generation of a choroid plexus carcinoma cell line; Children’s Cancer Hospital Egypt (CCHE)-45, which is characterized by the constitutive formation of aggresomes. When examining the autophagy pathway as the main route for aggresomes clearance, CCHE-45 cells displayed increased autophagy flux mediated by MAP1LC3B. MAP1LC3A-Variant1 gene expression was silenced by promoter methylation. Restoring MAP1LC3A-Variant1 expression resulted in the formation of MAP1LC3A positive autophagosmes and the disruption of the aggresomes' vimentin cage independent of MAP1LC3B positive autophagosomes. Our data supports the notion that basal quality control autophagy and vimentin cage clearance in CCHE-45 are mediated by MAP1LC3A. Hence we propose that absence of MAP1LC3A disrupts the autophagic pathway and leads to the failure of aggresome vimentin cage degradation. Consequently, this could represent a targetable pathway in autophagy-dependent cancers.
format	article
author	Marwa Nassar Heba Samaha Myret Ghabriel Maha Yehia Hala Taha Sherin Salem Khaled Shaaban Mariam Omar Nabil Ahmed Shahenda El-Naggar
author_facet	Marwa Nassar Heba Samaha Myret Ghabriel Maha Yehia Hala Taha Sherin Salem Khaled Shaaban Mariam Omar Nabil Ahmed Shahenda El-Naggar
author_sort	Marwa Nassar
title	LC3A Silencing Hinders Aggresome Vimentin Cage Clearance in Primary Choroid Plexus Carcinoma
title_short	LC3A Silencing Hinders Aggresome Vimentin Cage Clearance in Primary Choroid Plexus Carcinoma
title_full	LC3A Silencing Hinders Aggresome Vimentin Cage Clearance in Primary Choroid Plexus Carcinoma
title_fullStr	LC3A Silencing Hinders Aggresome Vimentin Cage Clearance in Primary Choroid Plexus Carcinoma
title_full_unstemmed	LC3A Silencing Hinders Aggresome Vimentin Cage Clearance in Primary Choroid Plexus Carcinoma
title_sort	lc3a silencing hinders aggresome vimentin cage clearance in primary choroid plexus carcinoma
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/b83392284343455b92814c88aef8b78b
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LC3A Silencing Hinders Aggresome Vimentin Cage Clearance in Primary Choroid Plexus Carcinoma

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