Molecular Pathways: Revisiting Glycogen Synthase Kinase-3β as a Target for the Treatment of Cancer
Amy Walz, Andrey Ugolkov, Sunandana Chandra, Alan Kozikowski, Benedito A Carneiro, Thomas V O'Halloran, Francis J Giles, Daniel D Billadeau, Andrew P Mazar, Amy Walz, Andrey Ugolkov, Sunandana Chandra, Alan Kozikowski, Benedito A Carneiro, Thomas V O'Halloran, Francis J Giles, Daniel D Billadeau, Andrew P Mazar
Abstract
Glycogen synthase kinase-3β (GSK-3β), a serine/threonine protein kinase, is a complex regulator of numerous cellular functions. GSK-3β is a unique kinase which is constitutively active in resting and nonstimulated cells. GSK-3β has been implicated in a wide range of diseases including neurodegeneration, inflammation and fibrosis, noninsulin-dependent diabetes mellitus, and cancer. It is a regulator of NF-κB-mediated survival of cancer cells, which provided a rationale for the development of GSK-3 inhibitors targeting malignant tumors. Recent studies, many of them reported over the past decade, have identified GSK-3β as a potential therapeutic target in more than 15 different types of cancer. Whereas only active GSK-3β is expressed in cancer cell nucleus, aberrant nuclear accumulation of GSK-3β has been identified as a hallmark of cancer cells in malignant tumors of different origin. This review focuses on the preclinical and clinical development of GSK-3 inhibitors and the potential therapeutic impact of targeting GSK-3β in human cancer. Clin Cancer Res; 23(8); 1891-7. ©2017 AACR.
Conflict of interest statement
Financial disclosures. No potential conflicts of interest were disclosed by the other authors.
©2017 American Association for Cancer Research.
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Source: PubMed