Wild-type and mutant p53 in cancer-related ferroptosis. A matter of stress management?
Cancer cells within tumor masses are chronically exposed to stress caused by nutrient deprivation, oxygen limitation, and high metabolic demand. They also accumulate hundreds of mutations, potentially generating aberrant proteins that can induce proteotoxic stress. Finally, cancer cells are exposed...
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Format: | Article |
Language: | English |
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Frontiers Media S.A.
2023-03-01
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Series: | Frontiers in Genetics |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1148192/full |
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author | Marco Corazzari Licio Collavin |
author_facet | Marco Corazzari Licio Collavin |
author_sort | Marco Corazzari |
collection | DOAJ |
description | Cancer cells within tumor masses are chronically exposed to stress caused by nutrient deprivation, oxygen limitation, and high metabolic demand. They also accumulate hundreds of mutations, potentially generating aberrant proteins that can induce proteotoxic stress. Finally, cancer cells are exposed to various damages during chemotherapy. In a growing tumor, transformed cells eventually adapt to these conditions, eluding the death-inducing outcomes of signaling cascades triggered by chronic stress. One such extreme outcome is ferroptosis, a form of iron-dependent non-apoptotic cell death mediated by lipid peroxidation. Not surprisingly, the tumor suppressor p53 is involved in this process, with evidence suggesting that it acts as a pro-ferroptotic factor and that its ferroptosis-inducing activity may be relevant for tumor suppression. Missense alterations of the TP53 gene are extremely frequent in human cancers and give rise to mutant p53 proteins (mutp53) that lose tumor suppressive function and can acquire powerful oncogenic activities. This suggests that p53 mutation provides a selective advantage during tumor progression, raising interesting questions on the impact of p53 mutant proteins in modulating the ferroptotic process. Here, we explore the role of p53 and its cancer-related mutants in ferroptosis, using a perspective centered on the resistance/sensitivity of cancer cells to exogenous and endogenous stress conditions that can trigger ferroptotic cell death. We speculate that an accurate molecular understanding of this particular axis may improve cancer treatment options. |
first_indexed | 2024-04-09T23:36:51Z |
format | Article |
id | doaj.art-022279fcf9cf4eb5a0690c15a4259261 |
institution | Directory Open Access Journal |
issn | 1664-8021 |
language | English |
last_indexed | 2024-04-09T23:36:51Z |
publishDate | 2023-03-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Genetics |
spelling | doaj.art-022279fcf9cf4eb5a0690c15a42592612023-03-20T04:56:53ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-03-011410.3389/fgene.2023.11481921148192Wild-type and mutant p53 in cancer-related ferroptosis. A matter of stress management?Marco Corazzari0Licio Collavin1Department of Health Sciences and Center for Translational Research on Autoimmune and Allergic Disease (CAAD), Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Piemonte Orientale, Novara, ItalyDepartment of Life Sciences, University of Trieste, Trieste, ItalyCancer cells within tumor masses are chronically exposed to stress caused by nutrient deprivation, oxygen limitation, and high metabolic demand. They also accumulate hundreds of mutations, potentially generating aberrant proteins that can induce proteotoxic stress. Finally, cancer cells are exposed to various damages during chemotherapy. In a growing tumor, transformed cells eventually adapt to these conditions, eluding the death-inducing outcomes of signaling cascades triggered by chronic stress. One such extreme outcome is ferroptosis, a form of iron-dependent non-apoptotic cell death mediated by lipid peroxidation. Not surprisingly, the tumor suppressor p53 is involved in this process, with evidence suggesting that it acts as a pro-ferroptotic factor and that its ferroptosis-inducing activity may be relevant for tumor suppression. Missense alterations of the TP53 gene are extremely frequent in human cancers and give rise to mutant p53 proteins (mutp53) that lose tumor suppressive function and can acquire powerful oncogenic activities. This suggests that p53 mutation provides a selective advantage during tumor progression, raising interesting questions on the impact of p53 mutant proteins in modulating the ferroptotic process. Here, we explore the role of p53 and its cancer-related mutants in ferroptosis, using a perspective centered on the resistance/sensitivity of cancer cells to exogenous and endogenous stress conditions that can trigger ferroptotic cell death. We speculate that an accurate molecular understanding of this particular axis may improve cancer treatment options.https://www.frontiersin.org/articles/10.3389/fgene.2023.1148192/fullhypoxiaautophagyUPRunfolded protein responsep53 tumor suppressorER stress |
spellingShingle | Marco Corazzari Licio Collavin Wild-type and mutant p53 in cancer-related ferroptosis. A matter of stress management? Frontiers in Genetics hypoxia autophagy UPR unfolded protein response p53 tumor suppressor ER stress |
title | Wild-type and mutant p53 in cancer-related ferroptosis. A matter of stress management? |
title_full | Wild-type and mutant p53 in cancer-related ferroptosis. A matter of stress management? |
title_fullStr | Wild-type and mutant p53 in cancer-related ferroptosis. A matter of stress management? |
title_full_unstemmed | Wild-type and mutant p53 in cancer-related ferroptosis. A matter of stress management? |
title_short | Wild-type and mutant p53 in cancer-related ferroptosis. A matter of stress management? |
title_sort | wild type and mutant p53 in cancer related ferroptosis a matter of stress management |
topic | hypoxia autophagy UPR unfolded protein response p53 tumor suppressor ER stress |
url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1148192/full |
work_keys_str_mv | AT marcocorazzari wildtypeandmutantp53incancerrelatedferroptosisamatterofstressmanagement AT liciocollavin wildtypeandmutantp53incancerrelatedferroptosisamatterofstressmanagement |