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Tumor Biology

, Volume 37, Issue 9, pp 11691–11700 | Cite as

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

  • Godfrey Grech
  • Shawn Baldacchino
  • Christian Saliba
  • Maria Pia Grixti
  • Robert Gauci
  • Vanessa Petroni
  • Anthony G. Fenech
  • Christian Scerri
Review

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.

Keywords

Molecular targets Phosphatase activation PP2A complex Breast cancer Colorectal cancer Kinase inhibitors Novel therapeutics 

Notes

Compliance with ethical standards

Conflicts of interest

None.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  1. 1.Department of Pathology, Faculty of Medicine & Surgery, Medical SchoolUniversity of MaltaMsidaMalta
  2. 2.Centre for Molecular Medicine and BiobankingUniversity of MaltaMsidaMalta
  3. 3.Department of Anatomy, Faculty of Medicine & SurgeryUniversity of MaltaMsidaMalta
  4. 4.Department of Clinical Pharmacology & Therapeutics, Faculty of Medicine & SurgeryUniversity of MaltaMsidaMalta
  5. 5.Department of Physiology and Biochemistry, Faculty of Medicine & SurgeryUniversity of MaltaMsidaMalta
  6. 6.Molecular Genetics ClinicMater Dei HospitalMsidaMalta

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