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Updated: Feb 24, 2026
Author Spotlight: Insights and Innovations in Gene Expression Manipulation Techniques for Choroid Plexus Research
Published on: June 16, 2023
LC3A Silencing Hinders Aggresome Vimentin Cage Clearance in Primary Choroid Plexus Carcinoma
Marwa Nassar1,2, Heba Samaha1, Myret Ghabriel1
1Tumor Biology Research Program, Basic Research Unit, Department of Research, Children's Cancer Hospital Egypt 57357, P.O Box 11441, 1 Seket Al-Emam Street, Cairo, Egypt.
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.
Insights
Misfolded proteins form aggresomes, cleared by autophagy. In CCHE-45 cells, MAP1LC3A deficiency impairs aggresome clearance, suggesting a targetable pathway in autophagy-dependent cancers.
Area of Science:
- Cell Biology
- Cancer Research
- Molecular Biology
Background:
- Aggresomes are cellular inclusions that sequester misfolded proteins.
- Autophagy is the primary mechanism for aggresome clearance.
- The role of specific MAP1LC3 isoforms in aggresome degradation is not fully understood.
Purpose of the Study:
- To investigate aggresome formation and clearance in a novel choroid plexus carcinoma cell line (CCHE-45).
- To elucidate the role of MAP1LC3A and MAP1LC3B in aggresome degradation via autophagy.
- To identify potential therapeutic targets in autophagy-dependent cancers.
Main Methods:
- Generation and characterization of the CCHE-45 cell line.
- Analysis of autophagy flux and MAP1LC3B activity.
- Gene silencing and restoration of MAP1LC3A-Variant1 expression.
- Microscopy to assess aggresome and vimentin cage integrity.
Main Results:
- CCHE-45 cells constitutively form aggresomes.
- Increased autophagy flux mediated by MAP1LC3B was observed.
- MAP1LC3A-Variant1 gene expression was silenced by promoter methylation.
- Restoring MAP1LC3A-Variant1 expression led to MAP1LC3A-positive autophagosomes and aggresome vimentin cage disruption.
- MAP1LC3A, not MAP1LC3B, mediated basal quality control autophagy and vimentin cage clearance.
Conclusions:
- Absence of MAP1LC3A disrupts the autophagic pathway, leading to failed aggresome vimentin cage degradation.
- MAP1LC3A plays a critical role in clearing aggresomes and their associated vimentin cages.
- Targeting the MAP1LC3A-mediated pathway could be a therapeutic strategy for autophagy-dependent cancers.
