Targeting GSK-3: a promising approach for cancer therapy?
Glycogen synthase kinase (GSK)-3 has emerged as one of the most attractive therapeutic targets for the treatment of multiple neurological diseases, including Alzheimer's, stroke and bipolar disorders, as well as noninsulin-dependent diabetes mellitus and inflammation. Although the prominent role of GSK-3 in the adenomatous polyposis coli (APC)-beta-catenin destruction complex implies that inhibition of GSK-3 could possibly lead to tumor promotion through the activation of beta-catenin, several recent studies have shed new light on the activity of GSK-3 in cancer and provide insight into the molecular mechanisms by which it regulates tumor cell proliferation and survival of multiple human malignancies. In fact, GSK-3beta is a critical regulator of nuclear factor (NF)kappaB nuclear activity, suggesting that inhibition of GSK-3beta could be effective in the treatment of a wide variety of tumors with constitutively active NFkappaB. Herein, the authors will discuss the current understanding of the role of GSK-3 in human cancer and its potential as a therapeutic target.
Division of Oncology Research, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
Andrei V
AV
Ougolkov
Daniel D
DD
Billadeau
D002241:Carbohydrates / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000494:pharmacology; D015195:Drug Design; D038362:Glycogen Synthase Kinase 3 / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009369:Neoplasms / Q000737:chemistry / Q000188:drug therapy*
D002241:Carbohydrates; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D016328:NF-kappa B; D038362:Glycogen Synthase Kinase 3