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PP2A and cancer epigenetics: a therapeutic opportunity waiting to happen

The epigenetic state of chromatin is altered by regulators which influence gene expression in response to environmental stimuli. While several post-translational modifications contribute to chromatin accessibility and transcriptional programs, our understanding of the role that specific phosphorylat...

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Autores principales: Tinsley, Samantha L, Allen-Petersen, Brittany L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8807117/
https://www.ncbi.nlm.nih.gov/pubmed/35118387
http://dx.doi.org/10.1093/narcan/zcac002
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author Tinsley, Samantha L
Allen-Petersen, Brittany L
author_facet Tinsley, Samantha L
Allen-Petersen, Brittany L
author_sort Tinsley, Samantha L
collection PubMed
description The epigenetic state of chromatin is altered by regulators which influence gene expression in response to environmental stimuli. While several post-translational modifications contribute to chromatin accessibility and transcriptional programs, our understanding of the role that specific phosphorylation sites play is limited. In cancer, kinases and phosphatases are commonly deregulated resulting in increased oncogenic signaling and loss of epigenetic regulation. Aberrant epigenetic states are known to promote cellular plasticity and the development of therapeutic resistance in many cancer types, highlighting the importance of these mechanisms to cancer cell phenotypes. Protein Phosphatase 2A (PP2A) is a heterotrimeric holoenzyme that targets a diverse array of cellular proteins. The composition of the PP2A complex influences its cellular targets and activity. For this reason, PP2A can be tumor suppressive or oncogenic depending on cellular context. Understanding the nuances of PP2A regulation and its effect on epigenetic alterations can lead to new therapeutic avenues that afford more specificity and contribute to the growth of personalized medicine in the oncology field. In this review, we summarize the known PP2A-regulated substrates and potential phosphorylation sites that contribute to cancer cell epigenetics and possible strategies to therapeutically leverage this phosphatase to suppress tumor growth.
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spelling pubmed-88071172022-02-02 PP2A and cancer epigenetics: a therapeutic opportunity waiting to happen Tinsley, Samantha L Allen-Petersen, Brittany L NAR Cancer Critical Reviews and Perspectives The epigenetic state of chromatin is altered by regulators which influence gene expression in response to environmental stimuli. While several post-translational modifications contribute to chromatin accessibility and transcriptional programs, our understanding of the role that specific phosphorylation sites play is limited. In cancer, kinases and phosphatases are commonly deregulated resulting in increased oncogenic signaling and loss of epigenetic regulation. Aberrant epigenetic states are known to promote cellular plasticity and the development of therapeutic resistance in many cancer types, highlighting the importance of these mechanisms to cancer cell phenotypes. Protein Phosphatase 2A (PP2A) is a heterotrimeric holoenzyme that targets a diverse array of cellular proteins. The composition of the PP2A complex influences its cellular targets and activity. For this reason, PP2A can be tumor suppressive or oncogenic depending on cellular context. Understanding the nuances of PP2A regulation and its effect on epigenetic alterations can lead to new therapeutic avenues that afford more specificity and contribute to the growth of personalized medicine in the oncology field. In this review, we summarize the known PP2A-regulated substrates and potential phosphorylation sites that contribute to cancer cell epigenetics and possible strategies to therapeutically leverage this phosphatase to suppress tumor growth. Oxford University Press 2022-02-01 /pmc/articles/PMC8807117/ /pubmed/35118387 http://dx.doi.org/10.1093/narcan/zcac002 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of NAR Cancer. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Critical Reviews and Perspectives
Tinsley, Samantha L
Allen-Petersen, Brittany L
PP2A and cancer epigenetics: a therapeutic opportunity waiting to happen
title PP2A and cancer epigenetics: a therapeutic opportunity waiting to happen
title_full PP2A and cancer epigenetics: a therapeutic opportunity waiting to happen
title_fullStr PP2A and cancer epigenetics: a therapeutic opportunity waiting to happen
title_full_unstemmed PP2A and cancer epigenetics: a therapeutic opportunity waiting to happen
title_short PP2A and cancer epigenetics: a therapeutic opportunity waiting to happen
title_sort pp2a and cancer epigenetics: a therapeutic opportunity waiting to happen
topic Critical Reviews and Perspectives
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8807117/
https://www.ncbi.nlm.nih.gov/pubmed/35118387
http://dx.doi.org/10.1093/narcan/zcac002
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