title: Protein phosphatase 2A: a target for anticancer therapy.
abstract: Protein phosphatase 2A (PP2A), one of the main serine-threonine phosphatases in mammalian cells, maintains cell homoeostasis by counteracting most of the kinase-driven intracellular signalling pathways. Unrestrained activation of oncogenic kinases together with inhibition of tumour suppressors is often required for development of cancer. PP2A has been shown to be genetically altered or functionally inactivated in many solid cancers and leukaemias, and is therefore a tumour suppressor. For example, the phosphatase activity of PP2A is suppressed in chronic myeloid leukaemia and other malignancies characterised by aberrant activity of oncogenic kinases. Preclinical studies show that pharmacological restoration of PP2A tumour-suppressor activity by PP2A-activating drugs (eg, FTY720) effectively antagonises cancer development and progression. Here, we discuss PP2A as a druggable tumour suppressor in view of the possible introduction of PP2A-activating drugs into anticancer therapeutic protocols.
authors: Human Cancer Genetics Program, Department of Molecular Virology, Immunology, and Medical Genetics, and Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210-2207, USA. danilo.perrotti@osumc.edu
authors: Danilo
authors: D
authors: Perrotti
authors: Paolo
authors: P
authors: Neviani
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015195:Drug Design; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000627:therapeutic use*; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D020536:Enzyme Activators; D054648:Protein Phosphatase 2
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