title: Dual-specificity MAP kinase phosphatases as targets of cancer treatment.
abstract: The protein tyrosine phosphatase family (PTP) contains a group of dual-specificity phosphatases (DUSPs) that regulate the activivity of MAP kinases (MAPKs), which are key effectors in the control of cell growth and survival in physiological and pathological processes, including cancer. These phosphatases, named as MKP-DUSPs, include the MAPK phosphatases (MKPs) as well as a group of small-size atypical DUSPs structurally and functionally related to the MKPs. MKP-DUSPs, in most of the cases, are direct inactivators of MAPKs by dephosphorylation of both the Thr and the Tyr regulatory residues at the MAPKs catalytic loop. In some other cases, MKP-DUSPs regulate the activity of MAPKs indirectly, acting through upstream MAPK pathways components. The active involvement of MKP-DUSPs in oncogenesis or resistance to cancer therapies is now well documented, making the search and validation of MKP-DUSPs inhibitors a prominent area in clinical cancer research. Here, we review the current knowledge on the role of MKP-DUSPs in human cancer, the status of the preclinical development and validation of specific MKP-DUSP inhibitors, and the potential of MKP-DUSPs as targets for anti-cancer drugs.
authors.affiliation: Centro de Investigación Príncipe Felipe, 46013 Valencia, Spain.
authors.forename: Caroline
authors.initials: C
authors.lastname: Nunes-Xavier
authors.forename: Carlos
authors.initials: C
authors.lastname: Romá-Mateo
authors.forename: Pablo
authors.initials: P
authors.lastname: Ríos
authors.forename: Céline
authors.initials: C
authors.lastname: Tárrega
authors.forename: Rocío
authors.initials: R
authors.lastname: Cejudo-Marín
authors.forename: Lydia
authors.initials: L
authors.lastname: Tabernero
authors.forename: Rafael
authors.initials: R
authors.lastname: Pulido
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D054639:Mitogen-Activated Protein Kinase Phosphatases