title: Pharmacological Activation of Protein Phosphatase 2 A (PP2A): A Novel Strategy to Fight Against Human Malignancies?
abstract: BACKGROUND
  The serine-threonine protein phosphatase 2A (PP2A) regulates multiple cell signaling cascades and its inactivation by viral oncoproteins, mutation of specific structural subunits or upregulation of the cellular endogenous inhibitors may contribute to malignant transformation by regulating specific phosphorylation events. Pharmacological modulation of PP2A activity is becoming an attractive strategy for cancer treatment. Some compounds targeting PP2A are able to induce PP2A reactivation and subsequent cell death in several types of cancer.
  
  
  METHODS
  We undertook a search of bibliographic databases for peer-reviewed articles focusing on the main item of the review. We selected articles published in indexed journals. The quality of retrieved papers was appraised using the standard bibliometric indicators.
  
  
  RESULTS
  One hundred and fourteen papers were included in the review. Twenty-seven papers gave an overview of structure and physiological role of PP2A. Twenty-five papers outlined the role of PP2A in tumor suppression. Forty papers analyzed the mechanism involved in PP2A reactivation by synthetic compounds, and twenty-two papers outlined the capability of natural compounds of restoring PP2A activity and how this could be beneficial.
  
  
  CONCLUSIONS
  Findings analyzed in this review underline the central role of PP2A as a regulator of cell growth and survival, hence its function as tumor suppressor. The discovery that some compounds, either synthetic or natural, are capable of reactivating PP2A opens up new perspectives for future strategies to fully exploit therapeutic potential in human cancer. Thus, this review could also be of particular interest to pharmaceutical or biotechnology companies for drug design and targeted delivery.
authors.affiliation: Department of Biomedical Sciences and Human Oncology, "Aldo Moro" University of Bari Medical School, Policlinico Piazza Giulio Cesare 11, 70124 Bari, Italy.
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Carratù
authors.forename: Anna
authors.initials: A
authors.lastname: Signorile
authors.forename: Domenico
authors.initials: D
authors.lastname: De Rasmo
authors.forename: Antonia
authors.initials: A
authors.lastname: Reale
authors.forename: Angelo
authors.initials: A
authors.lastname: Vacca
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use; D001688:Biological Products / Q000737:chemistry / Q000627:therapeutic use; D000069286:Bortezomib / Q000737:chemistry / Q000627:therapeutic use; D000068876:Fingolimod Hydrochloride / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D007166:Immunosuppressive Agents; D000069286:Bortezomib; D051057:Proto-Oncogene Proteins c-akt; D054648:Protein Phosphatase 2; D000068876:Fingolimod Hydrochloride