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The Contribution of Oxidative Stress to NF1-Altered Tumors

The neurofibromatosis-1 gene (NF1) was initially characterized because its germline mutation is responsible for an inherited syndromic disease predisposing tumor development, in particular neurofibromas but also various malignancies. Recently, large-scale tumor sequencing efforts have demonstrated N...

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Autores principales: Kuhn, Elisabetta, Natacci, Federica, Corbo, Massimo, Pisani, Luigi, Ferrero, Stefano, Bulfamante, Gaetano, Gambini, Donatella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10451967/
https://www.ncbi.nlm.nih.gov/pubmed/37627552
http://dx.doi.org/10.3390/antiox12081557
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author Kuhn, Elisabetta
Natacci, Federica
Corbo, Massimo
Pisani, Luigi
Ferrero, Stefano
Bulfamante, Gaetano
Gambini, Donatella
author_facet Kuhn, Elisabetta
Natacci, Federica
Corbo, Massimo
Pisani, Luigi
Ferrero, Stefano
Bulfamante, Gaetano
Gambini, Donatella
author_sort Kuhn, Elisabetta
collection PubMed
description The neurofibromatosis-1 gene (NF1) was initially characterized because its germline mutation is responsible for an inherited syndromic disease predisposing tumor development, in particular neurofibromas but also various malignancies. Recently, large-scale tumor sequencing efforts have demonstrated NF1 as one of the most frequently mutated genes in human cancer, being mutated in approximately 5–10% of all tumors, especially in malignant peripheral nerve sheath tumors and different skin tumors. NF1 acts as a tumor suppressor gene that encodes neurofibromin, a large protein that controls neoplastic transformation through several molecular mechanisms. On the other hand, neurofibromin loss due to NF1 biallelic inactivation induces tumorigenic hyperactivation of Ras and mTOR signaling pathways. Moreover, neurofibromin controls actin cytoskeleton structure and the metaphase–anaphase transition. Consequently, neurofibromin deficiency favors cell mobility and proliferation as well as chromosomal instability and aneuploidy, respectively. Growing evidence supports the role of oxidative stress in NF1-related tumorigenesis. Neurofibromin loss induces oxidative stress both directly and through Ras and mTOR signaling activation. Notably, innovative therapeutic approaches explore drug combinations that further increase reactive oxygen species to boost the oxidative unbalance of NF1-altered cancer cells. In our paper, we review NF1-related tumors and their pathogenesis, highlighting the twofold contribution of oxidative stress, both tumorigenic and therapeutic.
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spelling pubmed-104519672023-08-26 The Contribution of Oxidative Stress to NF1-Altered Tumors Kuhn, Elisabetta Natacci, Federica Corbo, Massimo Pisani, Luigi Ferrero, Stefano Bulfamante, Gaetano Gambini, Donatella Antioxidants (Basel) Review The neurofibromatosis-1 gene (NF1) was initially characterized because its germline mutation is responsible for an inherited syndromic disease predisposing tumor development, in particular neurofibromas but also various malignancies. Recently, large-scale tumor sequencing efforts have demonstrated NF1 as one of the most frequently mutated genes in human cancer, being mutated in approximately 5–10% of all tumors, especially in malignant peripheral nerve sheath tumors and different skin tumors. NF1 acts as a tumor suppressor gene that encodes neurofibromin, a large protein that controls neoplastic transformation through several molecular mechanisms. On the other hand, neurofibromin loss due to NF1 biallelic inactivation induces tumorigenic hyperactivation of Ras and mTOR signaling pathways. Moreover, neurofibromin controls actin cytoskeleton structure and the metaphase–anaphase transition. Consequently, neurofibromin deficiency favors cell mobility and proliferation as well as chromosomal instability and aneuploidy, respectively. Growing evidence supports the role of oxidative stress in NF1-related tumorigenesis. Neurofibromin loss induces oxidative stress both directly and through Ras and mTOR signaling activation. Notably, innovative therapeutic approaches explore drug combinations that further increase reactive oxygen species to boost the oxidative unbalance of NF1-altered cancer cells. In our paper, we review NF1-related tumors and their pathogenesis, highlighting the twofold contribution of oxidative stress, both tumorigenic and therapeutic. MDPI 2023-08-04 /pmc/articles/PMC10451967/ /pubmed/37627552 http://dx.doi.org/10.3390/antiox12081557 Text en © 2023 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
Kuhn, Elisabetta
Natacci, Federica
Corbo, Massimo
Pisani, Luigi
Ferrero, Stefano
Bulfamante, Gaetano
Gambini, Donatella
The Contribution of Oxidative Stress to NF1-Altered Tumors
title The Contribution of Oxidative Stress to NF1-Altered Tumors
title_full The Contribution of Oxidative Stress to NF1-Altered Tumors
title_fullStr The Contribution of Oxidative Stress to NF1-Altered Tumors
title_full_unstemmed The Contribution of Oxidative Stress to NF1-Altered Tumors
title_short The Contribution of Oxidative Stress to NF1-Altered Tumors
title_sort contribution of oxidative stress to nf1-altered tumors
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10451967/
https://www.ncbi.nlm.nih.gov/pubmed/37627552
http://dx.doi.org/10.3390/antiox12081557
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