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The Interplay of Microtubules with Mitochondria–ER Contact Sites (MERCs) in Glioblastoma

Gliomas are heterogeneous neoplasms, classified into grade I to IV according to their malignancy and the presence of specific histological/molecular hallmarks. The higher grade of glioma is known as glioblastoma (GB). Although progress has been made in surgical and radiation treatments, its clinical...

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Autores principales: Grespi, Francesca, Vianello, Caterina, Cagnin, Stefano, Giacomello, Marta, De Mario, Agnese
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9030160/
https://www.ncbi.nlm.nih.gov/pubmed/35454156
http://dx.doi.org/10.3390/biom12040567
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author Grespi, Francesca
Vianello, Caterina
Cagnin, Stefano
Giacomello, Marta
De Mario, Agnese
author_facet Grespi, Francesca
Vianello, Caterina
Cagnin, Stefano
Giacomello, Marta
De Mario, Agnese
author_sort Grespi, Francesca
collection PubMed
description Gliomas are heterogeneous neoplasms, classified into grade I to IV according to their malignancy and the presence of specific histological/molecular hallmarks. The higher grade of glioma is known as glioblastoma (GB). Although progress has been made in surgical and radiation treatments, its clinical outcome is still unfavorable. The invasive properties of GB cells and glioma aggressiveness are linked to the reshaping of the cytoskeleton. Recent works suggest that the different susceptibility of GB cells to antitumor immune response is also associated with the extent and function of mitochondria–ER contact sites (MERCs). The presence of MERCs alterations could also explain the mitochondrial defects observed in GB models, including abnormalities of energy metabolism and disruption of apoptotic and calcium signaling. Based on this evidence, the question arises as to whether a MERCs–cytoskeleton crosstalk exists, and whether GB progression is linked to an altered cytoskeleton–MERCs interaction. To address this possibility, in this review we performed a meta-analysis to compare grade I and grade IV GB patients. From this preliminary analysis, we found that GB samples (grade IV) are characterized by altered expression of cytoskeletal and MERCs related genes. Among them, the cytoskeleton-associated protein 4 (CKAP4 or CLIMP-63) appears particularly interesting as it encodes a MERCs protein controlling the ER anchoring to microtubules (MTs). Although further in-depth analyses remain necessary, this perspective review may provide new hints to better understand GB molecular etiopathogenesis, by suggesting that cytoskeletal and MERCs alterations cooperate to exacerbate the cellular phenotype of high-grade GB and that MERCs players can be exploited as novel biomarkers/targets to enhance the current therapy for GB.
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spelling pubmed-90301602022-04-23 The Interplay of Microtubules with Mitochondria–ER Contact Sites (MERCs) in Glioblastoma Grespi, Francesca Vianello, Caterina Cagnin, Stefano Giacomello, Marta De Mario, Agnese Biomolecules Review Gliomas are heterogeneous neoplasms, classified into grade I to IV according to their malignancy and the presence of specific histological/molecular hallmarks. The higher grade of glioma is known as glioblastoma (GB). Although progress has been made in surgical and radiation treatments, its clinical outcome is still unfavorable. The invasive properties of GB cells and glioma aggressiveness are linked to the reshaping of the cytoskeleton. Recent works suggest that the different susceptibility of GB cells to antitumor immune response is also associated with the extent and function of mitochondria–ER contact sites (MERCs). The presence of MERCs alterations could also explain the mitochondrial defects observed in GB models, including abnormalities of energy metabolism and disruption of apoptotic and calcium signaling. Based on this evidence, the question arises as to whether a MERCs–cytoskeleton crosstalk exists, and whether GB progression is linked to an altered cytoskeleton–MERCs interaction. To address this possibility, in this review we performed a meta-analysis to compare grade I and grade IV GB patients. From this preliminary analysis, we found that GB samples (grade IV) are characterized by altered expression of cytoskeletal and MERCs related genes. Among them, the cytoskeleton-associated protein 4 (CKAP4 or CLIMP-63) appears particularly interesting as it encodes a MERCs protein controlling the ER anchoring to microtubules (MTs). Although further in-depth analyses remain necessary, this perspective review may provide new hints to better understand GB molecular etiopathogenesis, by suggesting that cytoskeletal and MERCs alterations cooperate to exacerbate the cellular phenotype of high-grade GB and that MERCs players can be exploited as novel biomarkers/targets to enhance the current therapy for GB. MDPI 2022-04-12 /pmc/articles/PMC9030160/ /pubmed/35454156 http://dx.doi.org/10.3390/biom12040567 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Grespi, Francesca
Vianello, Caterina
Cagnin, Stefano
Giacomello, Marta
De Mario, Agnese
The Interplay of Microtubules with Mitochondria–ER Contact Sites (MERCs) in Glioblastoma
title The Interplay of Microtubules with Mitochondria–ER Contact Sites (MERCs) in Glioblastoma
title_full The Interplay of Microtubules with Mitochondria–ER Contact Sites (MERCs) in Glioblastoma
title_fullStr The Interplay of Microtubules with Mitochondria–ER Contact Sites (MERCs) in Glioblastoma
title_full_unstemmed The Interplay of Microtubules with Mitochondria–ER Contact Sites (MERCs) in Glioblastoma
title_short The Interplay of Microtubules with Mitochondria–ER Contact Sites (MERCs) in Glioblastoma
title_sort interplay of microtubules with mitochondria–er contact sites (mercs) in glioblastoma
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9030160/
https://www.ncbi.nlm.nih.gov/pubmed/35454156
http://dx.doi.org/10.3390/biom12040567
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