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

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 for...

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Autores principales: Nassar, Marwa, Samaha, Heba, Ghabriel, Myret, Yehia, Maha, Taha, Hala, Salem, Sherin, Shaaban, Khaled, Omar, Mariam, Ahmed, Nabil, El-Naggar, Shahenda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5556083/
https://www.ncbi.nlm.nih.gov/pubmed/28808307
http://dx.doi.org/10.1038/s41598-017-07403-5
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author Nassar, Marwa
Samaha, Heba
Ghabriel, Myret
Yehia, Maha
Taha, Hala
Salem, Sherin
Shaaban, Khaled
Omar, Mariam
Ahmed, Nabil
El-Naggar, Shahenda
author_facet Nassar, Marwa
Samaha, Heba
Ghabriel, Myret
Yehia, Maha
Taha, Hala
Salem, Sherin
Shaaban, Khaled
Omar, Mariam
Ahmed, Nabil
El-Naggar, Shahenda
author_sort Nassar, Marwa
collection PubMed
description 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.
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spelling pubmed-55560832017-08-16 LC3A Silencing Hinders Aggresome Vimentin Cage Clearance in Primary Choroid Plexus Carcinoma Nassar, Marwa Samaha, Heba Ghabriel, Myret Yehia, Maha Taha, Hala Salem, Sherin Shaaban, Khaled Omar, Mariam Ahmed, Nabil El-Naggar, Shahenda Sci Rep Article 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. Nature Publishing Group UK 2017-08-14 /pmc/articles/PMC5556083/ /pubmed/28808307 http://dx.doi.org/10.1038/s41598-017-07403-5 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Nassar, Marwa
Samaha, Heba
Ghabriel, Myret
Yehia, Maha
Taha, Hala
Salem, Sherin
Shaaban, Khaled
Omar, Mariam
Ahmed, Nabil
El-Naggar, Shahenda
LC3A Silencing Hinders Aggresome Vimentin Cage Clearance in Primary Choroid Plexus Carcinoma
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5556083/
https://www.ncbi.nlm.nih.gov/pubmed/28808307
http://dx.doi.org/10.1038/s41598-017-07403-5
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