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

Overview

Journal Sci Rep

Specialty Science

Date 2017 Aug 16

PMID 28808307

Citations 13

Authors

Marwa Nassar

Heba Samaha

Myret Ghabriel

Maha Yehia

Hala Taha

Sherin Salem

Khaled Shaaban

Mariam Omar

Nabil Ahmed

Shahenda El-Naggar

Affiliations

Soon will be listed here.

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.

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