title: Deregulation of the protein phosphatase 2A, PP2A in cancer: complexity and therapeutic options.
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.
authors.affiliation: Department of Pathology, Faculty of Medicine & Surgery, Medical School, University of Malta, Msida, MSD2090, Malta. godfrey.grech@um.edu.mt.
authors.forename: Godfrey
authors.identifier: http://orcid.org/0000-0003-4502-8237
authors.initials: G
authors.lastname: Grech
authors.affiliation: Department of Pathology, Faculty of Medicine & Surgery, Medical School, University of Malta, Msida, MSD2090, Malta.
authors.forename: Shawn
authors.initials: S
authors.lastname: Baldacchino
authors.affiliation: Centre for Molecular Medicine and Biobanking, University of Malta, Msida, Malta.
authors.forename: Christian
authors.initials: C
authors.lastname: Saliba
authors.affiliation: Department of Pathology, Faculty of Medicine & Surgery, Medical School, University of Malta, Msida, MSD2090, Malta.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Grixti
authors.affiliation: Department of Pathology, Faculty of Medicine & Surgery, Medical School, University of Malta, Msida, MSD2090, Malta.
authors.forename: Robert
authors.initials: R
authors.lastname: Gauci
authors.affiliation: Department of Anatomy, Faculty of Medicine & Surgery, University of Malta, Msida, Malta.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Petroni
authors.affiliation: Department of Clinical Pharmacology & Therapeutics, Faculty of Medicine & Surgery, University of Malta, Msida, Malta.
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Fenech
authors.affiliation: Department of Physiology and Biochemistry, Faculty of Medicine & Surgery, University of Malta, Msida, Malta.|Molecular Genetics Clinic, Mater Dei Hospital, Msida, Malta.
authors.forename: Christian
authors.initials: C
authors.lastname: Scerri
mesh_terms: D000818:Animals; D004789:Enzyme Activation; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D021122:Protein Subunits
chemical_list: D021122:Protein Subunits; D054648:Protein Phosphatase 2
keywords: Breast cancer; Colorectal cancer; Kinase inhibitors; Molecular targets; Novel therapeutics; PP2A complex; Phosphatase activation