GSK-3 as potential target for therapeutic intervention in cancer

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,...

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Published in:Oncotarget 2014-05, Vol.5 (10), p.2881-2911
Main Authors: McCubrey, James A, Steelman, Linda S, Bertrand, Fred E, Davis, Nicole M, Sokolosky, Melissa, Abrams, Steve L, Montalto, Giuseppe, D'Assoro, Antonino B, Libra, Massimo, Nicoletti, Ferdinando, Maestro, Roberta, Basecke, Jorg, Rakus, Dariusz, Gizak, Agnieszka, Demidenko, Zoya N, Cocco, Lucio, Martelli, Alberto M, Cervello, Melchiorre
Format: Article
Language:English
Subjects:
Animals
Glycogen Synthase Kinase 3 - physiology
Humans
Neoplasms - enzymology
Neoplasms - genetics
Neoplasms - physiopathology
Review
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Summary: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.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.2037