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Tumor Biology
Published in: Tumor Biology 9/2016

01-09-2016 | Review

Deregulation of the protein phosphatase 2A, PP2A in cancer: complexity and therapeutic options

Authors: Godfrey Grech, Shawn Baldacchino, Christian Saliba, Maria Pia Grixti, Robert Gauci, Vanessa Petroni, Anthony G. Fenech, Christian Scerri

Published in: Tumor Biology | Issue 9/2016

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Abstract

The complexity of the phosphatase, PP2A, is being unravelled and current research is increasingly providing information on the association of deregulated PP2A function with cancer initiation and progression. It has been reported that decreased activity of PP2A is a recurrent observation in many types of cancer, including colorectal and breast cancer (Baldacchino et al. EPMA J. 5:3, 2014; Cristobal et al. Mol Cancer Ther. 13:938–947, 2014). Since deregulation of PP2A and its regulatory subunits is a common event in cancer, PP2A is a potential target for therapy (Baldacchino et al. EPMA J. 5:3, 2014). In this review, the structural components of the PP2A complex are described, giving an in depth overview of the diversity of regulatory subunits. Regulation of the active PP2A trimeric complex, through phosphorylation and methylation, can be targeted using known compounds, to reactivate the complex. The endogenous inhibitors of the PP2A complex are highly deregulated in cancer, representing cases that are eligible to PP2A-activating drugs. Pharmacological opportunities to target low PP2A activity are available and preclinical data support the efficacy of these drugs, but clinical trials are lacking. We highlight the importance of PP2A deregulation in cancer and the current trends in targeting the phosphatase.
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Metadata
Title
Deregulation of the protein phosphatase 2A, PP2A in cancer: complexity and therapeutic options
Authors
Godfrey Grech
Shawn Baldacchino
Christian Saliba
Maria Pia Grixti
Robert Gauci
Vanessa Petroni
Anthony G. Fenech
Christian Scerri
Publication date
01-09-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 9/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-016-5145-4

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