title: GSK-3 as potential target for therapeutic intervention in cancer.
abstract: The serine/threonine kinase glycogen synthase kinase-3 (GSK-3) was initially identified and studied in the regulation of glycogen synthesis. GSK-3 functions in a wide range of cellular processes. Aberrant activity of GSK-3 has been implicated in many human pathologies including: bipolar depression, Alzheimer's disease, Parkinson's disease, cancer, non-insulin-dependent diabetes mellitus (NIDDM) and others. In some cases, suppression of GSK-3 activity by phosphorylation by Akt and other kinases has been associated with cancer progression. In these cases, GSK-3 has tumor suppressor functions. In other cases, GSK-3 has been associated with tumor progression by stabilizing components of the beta-catenin complex. In these situations, GSK-3 has oncogenic properties. While many inhibitors to GSK-3 have been developed, their use remains controversial because of the ambiguous role of GSK-3 in cancer development. In this review, we will focus on the diverse roles that GSK-3 plays in various human cancers, in particular in solid tumors. Recently, GSK-3 has also been implicated in the generation of cancer stem cells in various cell types. We will also discuss how this pivotal kinase interacts with multiple signaling pathways such as: PI3K/PTEN/Akt/mTORC1, Ras/Raf/MEK/ERK, Wnt/beta-catenin, Hedgehog, Notch and others.
authors.affiliation: Department of Microbiology and Immunology,Brody School of Medicine at East Carolina University Greenville, NC 27858 USA.
authors.forename: James A
authors.initials: JA
authors.lastname: McCubrey
authors.forename: Linda S
authors.initials: LS
authors.lastname: Steelman
authors.forename: Fred E
authors.initials: FE
authors.lastname: Bertrand
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Davis
authors.forename: Melissa
authors.initials: M
authors.lastname: Sokolosky
authors.forename: Steve L
authors.initials: SL
authors.lastname: Abrams
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Montalto
authors.forename: Antonino B
authors.initials: AB
authors.lastname: D'Assoro
authors.forename: Massimo
authors.initials: M
authors.lastname: Libra
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
authors.forename: Roberta
authors.initials: R
authors.lastname: Maestro
authors.forename: Jorg
authors.initials: J
authors.lastname: Basecke
authors.forename: Dariusz
authors.initials: D
authors.lastname: Rakus
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gizak
authors.forename: Zoya N
authors.initials: ZN
authors.lastname: Demidenko
authors.forename: Lucio
authors.initials: L
authors.lastname: Cocco
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Martelli
authors.forename: Melchiorre
authors.initials: M
authors.lastname: Cervello
mesh_terms: D000818:Animals; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology
chemical_list: D038362:Glycogen Synthase Kinase 3