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- Title
Targeting GSK3 and Associated Signaling Pathways Involved in Cancer.
- Authors
Duda, Przemysław; Akula, Shaw M.; Abrams, Stephen L.; Steelman, Linda S.; Martelli, Alberto M.; Cocco, Lucio; Ratti, Stefano; Candido, Saverio; Libra, Massimo; Montalto, Giuseppe; Cervello, Melchiorre; Gizak, Agnieszka; Rakus, Dariusz; McCubrey, James A.
- Abstract
Glycogen synthase kinase 3 (GSK-3) is a serine/threonine (S/T) protein kinase. Although GSK-3 originally was identified to have functions in regulation of glycogen synthase, it was subsequently determined to have roles in multiple normal biochemical processes as well as various disease conditions. GSK-3 is sometimes referred to as a moonlighting protein due to the multiple substrates and processes which it controls. Frequently, when GSK-3 phosphorylates proteins, they are targeted for degradation. GSK-3 is often considered a component of the PI3K/PTEN/AKT/GSK-3/mTORC1 pathway as GSK-3 is frequently phosphorylated by AKT which regulates its inactivation. AKT is often active in human cancer and hence, GSK-3 is often inactivated. Moreover, GSK-3 also interacts with WNT/β-catenin signaling and β-catenin and other proteins in this pathway are targets of GSK-3. GSK-3 can modify NF-κB activity which is often expressed at high levels in cancer cells. Multiple pharmaceutical companies developed small molecule inhibitors to suppress GSK-3 activity. In addition, various natural products will modify GSK-3 activity. This review will focus on the effects of small molecule inhibitors and natural products on GSK-3 activity and provide examples where these compounds were effective in suppressing cancer growth.
- Subjects
GLYCOGEN synthase kinase-3; GLYCOGEN synthase kinase; SMALL molecules; PROTEIN kinases; NATURAL products; TUMOR growth
- Publication
Cells (2073-4409), 2020, Vol 9, Issue 5, p1110
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells9051110