title: Targeting DUSPs in glioblastomas - wielding a double-edged sword?
abstract: Several dual-specificity phosphatases (DUSPs) that play key roles in the direct or indirect inactivation of different MAP kinases (MAPKs) have been implicated in human cancers over the past decade. This has led to a growing interest in identifying DUSPs and their specific inhibitors for further testing and validation as therapeutic targets in human cancers. However, the lack of understanding of the complex regulatory mechanisms and cross-talks between MAPK signaling pathways, combined with the fact that DUSPs can act as a double-edged sword in cancer progression, calls for a more careful and thorough investigation. Among the various types of brain cancer, glioblastoma multiforme (GBM) is notorious for its aggressiveness and resistance to current treatment modalities. This has led to the search for new molecular targets, particularly those involving various signaling pathways. DUSPs appear to be a promising target, but much more information on DUSP targets and their effects on GBM is needed before potential therapies can be developed, tested, and validated. This review identifies and summarize the specific roles of DUSP1, DUSP4, DUSP6 and DUSP26 that have been implicated in GBM.
authors.affiliation: Department of Natural and Health Sciences, Southeastern University, Lakeland, Florida, 33801, USA.
authors.forename: Sheila
authors.initials: S
authors.lastname: Prabhakar
authors.forename: Swapna
authors.initials: S
authors.lastname: Asuthkar
authors.forename: William
authors.initials: W
authors.lastname: Lee
authors.forename: Srinivasulu
authors.initials: S
authors.lastname: Chigurupati
authors.forename: Eleonora
authors.initials: E
authors.lastname: Zakharian
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Tsung
authors.forename: Kiran Kumar
authors.initials: KK
authors.lastname: Velpula
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D055808:Drug Discovery; D054637:Dual-Specificity Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005909:Glioblastoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D054637:Dual-Specificity Phosphatases
keywords: brain/nervous system; cancer; tumor suppressor