The Contribution of Oxidative Stress to <i>NF1</i>-Altered Tumors
The neurofibromatosis-1 gene (<i>NF1</i>) 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...
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| Main Authors: | , , , , , , |
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| Format: | Book |
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MDPI AG,
2023-08-01T00:00:00Z.
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| Summary: | The neurofibromatosis-1 gene (<i>NF1</i>) 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 <i>NF1</i> 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. <i>NF1</i> 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 <i>NF1</i> 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 <i>NF1</i>-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 <i>NF1</i>-altered cancer cells. In our paper, we review <i>NF1</i>-related tumors and their pathogenesis, highlighting the twofold contribution of oxidative stress, both tumorigenic and therapeutic. |
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| Item Description: | 10.3390/antiox12081557 2076-3921 |