Targeting EZH2 in Cancer: Mechanisms, Pathways, and Therapeutic Potential

Enhancer of zeste homolog 2 (EZH2) is a methyltransferase involved in cell cycle regulation, cell differentiation, and cell death and plays a role in modulating the immune response. Although it mainly functions by catalyzing the tri-methylation of H3 histone on K27 (H3K27), to inhibit the transcript...

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Main Authors: Maria Saveria Gilardini Montani, Rossella Benedetti, Mara Cirone
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/29/24/5817
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author Maria Saveria Gilardini Montani
Rossella Benedetti
Mara Cirone
author_facet Maria Saveria Gilardini Montani
Rossella Benedetti
Mara Cirone
author_sort Maria Saveria Gilardini Montani
collection DOAJ
description Enhancer of zeste homolog 2 (EZH2) is a methyltransferase involved in cell cycle regulation, cell differentiation, and cell death and plays a role in modulating the immune response. Although it mainly functions by catalyzing the tri-methylation of H3 histone on K27 (H3K27), to inhibit the transcription of target genes, EZH2 can directly methylate several transcription factors or form complexes with them, regulating their functions. EZH2 expression/activity is often dysregulated in cancer, contributing to carcinogenesis and immune escape, thereby representing an important target in anti-cancer therapy. This review summarizes some of the mechanisms through which EZH2 regulates the expression and function of tumor suppressor genes and oncogenic molecules such as STAT3, mutant p53, and c-Myc and how it modulates the anti-cancer immune response. The influence of posttranslational modifications on EZH2 activity and stability and the possible strategies leading to its inhibition are also reviewed.
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spelling doaj-art-33ac5686d2044792ba5eff6802df12c22025-08-20T02:39:41ZengMDPI AGMolecules1420-30492024-12-012924581710.3390/molecules29245817Targeting EZH2 in Cancer: Mechanisms, Pathways, and Therapeutic PotentialMaria Saveria Gilardini Montani0Rossella Benedetti1Mara Cirone2Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyEnhancer of zeste homolog 2 (EZH2) is a methyltransferase involved in cell cycle regulation, cell differentiation, and cell death and plays a role in modulating the immune response. Although it mainly functions by catalyzing the tri-methylation of H3 histone on K27 (H3K27), to inhibit the transcription of target genes, EZH2 can directly methylate several transcription factors or form complexes with them, regulating their functions. EZH2 expression/activity is often dysregulated in cancer, contributing to carcinogenesis and immune escape, thereby representing an important target in anti-cancer therapy. This review summarizes some of the mechanisms through which EZH2 regulates the expression and function of tumor suppressor genes and oncogenic molecules such as STAT3, mutant p53, and c-Myc and how it modulates the anti-cancer immune response. The influence of posttranslational modifications on EZH2 activity and stability and the possible strategies leading to its inhibition are also reviewed.https://www.mdpi.com/1420-3049/29/24/5817EZH2methylationoncogenic pathwaysimmune escape and EZH2 inhibitors
spellingShingle Maria Saveria Gilardini Montani
Rossella Benedetti
Mara Cirone
Targeting EZH2 in Cancer: Mechanisms, Pathways, and Therapeutic Potential
Molecules
EZH2
methylation
oncogenic pathways
immune escape and EZH2 inhibitors
title Targeting EZH2 in Cancer: Mechanisms, Pathways, and Therapeutic Potential
title_full Targeting EZH2 in Cancer: Mechanisms, Pathways, and Therapeutic Potential
title_fullStr Targeting EZH2 in Cancer: Mechanisms, Pathways, and Therapeutic Potential
title_full_unstemmed Targeting EZH2 in Cancer: Mechanisms, Pathways, and Therapeutic Potential
title_short Targeting EZH2 in Cancer: Mechanisms, Pathways, and Therapeutic Potential
title_sort targeting ezh2 in cancer mechanisms pathways and therapeutic potential
topic EZH2
methylation
oncogenic pathways
immune escape and EZH2 inhibitors
url https://www.mdpi.com/1420-3049/29/24/5817
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AT rossellabenedetti targetingezh2incancermechanismspathwaysandtherapeuticpotential
AT maracirone targetingezh2incancermechanismspathwaysandtherapeuticpotential