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Protein phosphatase 2A (PP2A): a key phosphatase in the progression of chronic obstructive pulmonary disease (COPD) to lung cancer

Lung cancer (LC) has the highest relative risk of development as a comorbidity of chronic obstructive pulmonary disease (COPD). The molecular mechanisms that mediate chronic inflammation and lung function impairment in COPD have been identified in LC. This suggests the two diseases are more linked t...

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Autores principales: Nader, Cassandra P., Cidem, Aylin, Verrills, Nicole M., Ammit, Alaina J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6798356/
https://www.ncbi.nlm.nih.gov/pubmed/31623614
http://dx.doi.org/10.1186/s12931-019-1192-x
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author Nader, Cassandra P.
Cidem, Aylin
Verrills, Nicole M.
Ammit, Alaina J.
author_facet Nader, Cassandra P.
Cidem, Aylin
Verrills, Nicole M.
Ammit, Alaina J.
author_sort Nader, Cassandra P.
collection PubMed
description Lung cancer (LC) has the highest relative risk of development as a comorbidity of chronic obstructive pulmonary disease (COPD). The molecular mechanisms that mediate chronic inflammation and lung function impairment in COPD have been identified in LC. This suggests the two diseases are more linked than once thought. Emerging data in relation to a key phosphatase, protein phosphatase 2A (PP2A), and its regulatory role in inflammatory and tumour suppression in both disease settings suggests that it may be critical in the progression of COPD to LC. In this review, we uncover the importance of the functional and active PP2A holoenzyme in the context of both diseases. We describe PP2A inactivation via direct and indirect means and explore the actions of two key PP2A endogenous inhibitors, cancerous inhibitor of PP2A (CIP2A) and inhibitor 2 of PP2A (SET), and the role they play in COPD and LC. We explain how dysregulation of PP2A in COPD creates a favourable inflammatory micro-environment and promotes the initiation and progression of tumour pathogenesis. Finally, we highlight PP2A as a druggable target in the treatment of COPD and LC and demonstrate the potential of PP2A re-activation as a strategy to halt COPD disease progression to LC. Although further studies are required to elucidate if PP2A activity in COPD is a causal link for LC progression, studies focused on the potential of PP2A reactivating agents to reduce the risk of LC formation in COPD patients will be pivotal in improving clinical outcomes for both COPD and LC patients in the future.
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spelling pubmed-67983562019-10-21 Protein phosphatase 2A (PP2A): a key phosphatase in the progression of chronic obstructive pulmonary disease (COPD) to lung cancer Nader, Cassandra P. Cidem, Aylin Verrills, Nicole M. Ammit, Alaina J. Respir Res Review Lung cancer (LC) has the highest relative risk of development as a comorbidity of chronic obstructive pulmonary disease (COPD). The molecular mechanisms that mediate chronic inflammation and lung function impairment in COPD have been identified in LC. This suggests the two diseases are more linked than once thought. Emerging data in relation to a key phosphatase, protein phosphatase 2A (PP2A), and its regulatory role in inflammatory and tumour suppression in both disease settings suggests that it may be critical in the progression of COPD to LC. In this review, we uncover the importance of the functional and active PP2A holoenzyme in the context of both diseases. We describe PP2A inactivation via direct and indirect means and explore the actions of two key PP2A endogenous inhibitors, cancerous inhibitor of PP2A (CIP2A) and inhibitor 2 of PP2A (SET), and the role they play in COPD and LC. We explain how dysregulation of PP2A in COPD creates a favourable inflammatory micro-environment and promotes the initiation and progression of tumour pathogenesis. Finally, we highlight PP2A as a druggable target in the treatment of COPD and LC and demonstrate the potential of PP2A re-activation as a strategy to halt COPD disease progression to LC. Although further studies are required to elucidate if PP2A activity in COPD is a causal link for LC progression, studies focused on the potential of PP2A reactivating agents to reduce the risk of LC formation in COPD patients will be pivotal in improving clinical outcomes for both COPD and LC patients in the future. BioMed Central 2019-10-17 2019 /pmc/articles/PMC6798356/ /pubmed/31623614 http://dx.doi.org/10.1186/s12931-019-1192-x Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Review
Nader, Cassandra P.
Cidem, Aylin
Verrills, Nicole M.
Ammit, Alaina J.
Protein phosphatase 2A (PP2A): a key phosphatase in the progression of chronic obstructive pulmonary disease (COPD) to lung cancer
title Protein phosphatase 2A (PP2A): a key phosphatase in the progression of chronic obstructive pulmonary disease (COPD) to lung cancer
title_full Protein phosphatase 2A (PP2A): a key phosphatase in the progression of chronic obstructive pulmonary disease (COPD) to lung cancer
title_fullStr Protein phosphatase 2A (PP2A): a key phosphatase in the progression of chronic obstructive pulmonary disease (COPD) to lung cancer
title_full_unstemmed Protein phosphatase 2A (PP2A): a key phosphatase in the progression of chronic obstructive pulmonary disease (COPD) to lung cancer
title_short Protein phosphatase 2A (PP2A): a key phosphatase in the progression of chronic obstructive pulmonary disease (COPD) to lung cancer
title_sort protein phosphatase 2a (pp2a): a key phosphatase in the progression of chronic obstructive pulmonary disease (copd) to lung cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6798356/
https://www.ncbi.nlm.nih.gov/pubmed/31623614
http://dx.doi.org/10.1186/s12931-019-1192-x
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