Epigenetic regulation of cancer stemness

Abstract Gene expression is finely controlled by the abundance and activation status of transcription factors and their regulators, as well as by a number of reversible modifications of DNA and histones that are commonly referred to as epigenetic marks. Such alterations (i.e., methylation, acetylati...

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Main Authors: Claudia Galassi, Gwenola Manic, Manel Esteller, Lorenzo Galluzzi, Ilio Vitale
Format: Article
Language:English
Published: Nature Publishing Group 2025-08-01
Series:Signal Transduction and Targeted Therapy
Online Access:https://doi.org/10.1038/s41392-025-02340-6
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author Claudia Galassi
Gwenola Manic
Manel Esteller
Lorenzo Galluzzi
Ilio Vitale
author_facet Claudia Galassi
Gwenola Manic
Manel Esteller
Lorenzo Galluzzi
Ilio Vitale
author_sort Claudia Galassi
collection DOAJ
description Abstract Gene expression is finely controlled by the abundance and activation status of transcription factors and their regulators, as well as by a number of reversible modifications of DNA and histones that are commonly referred to as epigenetic marks. Such alterations (i.e., methylation, acetylation, and ubiquitination) are catalyzed by an array of dedicated enzymes with antagonistic activity, including methyltransferases and demethylases, acetyltransferases and deacetylases, as well as ubiquitin ligases and deubiquitinating enzymes. The epigenetic control of transcription is critical not only for embryonic and postembryonic development but also for the preservation of homeostasis in all adult tissues. In line with this notion, epigenetic defects have been associated with a variety of human disorders, including (but not limited to) congenital conditions as well as multiple hematological and solid tumors. Here, we provide an in-depth discussion of the impact of epigenetic alterations on cancer stemness, i.e., the ability of a small population of poorly differentiated malignant cells to (1) self-renew while generating a more differentiated progeny, and (2) exhibit superior tumor initiating/repopulating potential along with exceptional plasticity and improved resistance to environmental and therapy-elicited stress. Moreover, we critically evaluate the potential and limitations of targeting epigenetic modifiers as a means to eradicate cancer stem cells for therapeutic purposes.
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spelling doaj-art-63f48ecec39a4298a2513f60ba9d08d12025-08-20T03:06:09ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352025-08-0110111910.1038/s41392-025-02340-6Epigenetic regulation of cancer stemnessClaudia Galassi0Gwenola Manic1Manel Esteller2Lorenzo Galluzzi3Ilio Vitale4Department of Pharmacology, Weill Cornell Medical CollegeItalian Institute for Genomic Medicine, c/o IRCSS CandioloCancer Epigenetics Group, Josep Carreras Leukemia Research Institute (IJC)Cancer Signaling and Microenvironment Program, Fox Chase Cancer CenterItalian Institute for Genomic Medicine, c/o IRCSS CandioloAbstract Gene expression is finely controlled by the abundance and activation status of transcription factors and their regulators, as well as by a number of reversible modifications of DNA and histones that are commonly referred to as epigenetic marks. Such alterations (i.e., methylation, acetylation, and ubiquitination) are catalyzed by an array of dedicated enzymes with antagonistic activity, including methyltransferases and demethylases, acetyltransferases and deacetylases, as well as ubiquitin ligases and deubiquitinating enzymes. The epigenetic control of transcription is critical not only for embryonic and postembryonic development but also for the preservation of homeostasis in all adult tissues. In line with this notion, epigenetic defects have been associated with a variety of human disorders, including (but not limited to) congenital conditions as well as multiple hematological and solid tumors. Here, we provide an in-depth discussion of the impact of epigenetic alterations on cancer stemness, i.e., the ability of a small population of poorly differentiated malignant cells to (1) self-renew while generating a more differentiated progeny, and (2) exhibit superior tumor initiating/repopulating potential along with exceptional plasticity and improved resistance to environmental and therapy-elicited stress. Moreover, we critically evaluate the potential and limitations of targeting epigenetic modifiers as a means to eradicate cancer stem cells for therapeutic purposes.https://doi.org/10.1038/s41392-025-02340-6
spellingShingle Claudia Galassi
Gwenola Manic
Manel Esteller
Lorenzo Galluzzi
Ilio Vitale
Epigenetic regulation of cancer stemness
Signal Transduction and Targeted Therapy
title Epigenetic regulation of cancer stemness
title_full Epigenetic regulation of cancer stemness
title_fullStr Epigenetic regulation of cancer stemness
title_full_unstemmed Epigenetic regulation of cancer stemness
title_short Epigenetic regulation of cancer stemness
title_sort epigenetic regulation of cancer stemness
url https://doi.org/10.1038/s41392-025-02340-6
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AT manelesteller epigeneticregulationofcancerstemness
AT lorenzogalluzzi epigeneticregulationofcancerstemness
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