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Cited by 284Wnt/β-catenin signaling in development and cancerPI3K/AKT/mTOR signaling in cancerSignaling Pathways in Disease

Targeting GSK3 and Associated Signaling Pathways Involved in Cancer

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Duda, Przemysław, Akula, Shaw M., Abrams, Stephen L., Steelman, Linda S., Martelli, Alberto M., Cocco, Lucio, Ratti, Stefano, Candido, Saverio +6 more·2020·Cells
DOI 10.3390/cells9051110PMC PMC7290852
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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.

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Authors
Duda, P., Akula, S. M., Abrams, S. L., Steelman, L. S., Martelli, A. M., Cocco, L., Ratti, S., Candido, S., Libra, M., Montalto, G., Cervello, M., Gizak, A., Rakus, D., & McCubrey, J. A.
Affiliations
  • University of Wrocław (PL)
  • East Carolina University (US)
  • University of Bologna (IT)
  • University of Catania (IT)
  • Institute for Biomedical Research and Innovation (IT)
Corresponding author
McCubrey, James A.
ORCID
Venue
Cells
Publisher
MDPI AG
Published
2020-04-30
Volume
9
Issue
5
Pages
1110
ISSN
2073-4409 (ISSN-L)
DOI
10.3390/cells9051110
PMC
PMC7290852
OpenAlex
W3021209014
Cited by
284
References
112
Citations by year
2026: 30 · 2025: 46 · 2024: 48 · 2023: 59 · 2022: 43 · 2021: 42 · 2020: 15 · 2019: 1
FWCI
3.85
Type
journal article
Language
en
Open access
Licence
Locations
  • Cells (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Brody School of Medicine (111110-668715-0000)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords
glycogen synthase kinase-3, GSK-3 inhibitors, small molecule inhibitors, natural products, cancer, PI3K/AKT/mTOR pathway, Wnt/β-catenin signaling, NF-κB, protein phosphorylation, moonlighting proteins
MeSH terms
Humans, Neoplasms, Phosphorylation, Protein Serine-Threonine Kinases, Glycogen Synthase Kinase 3, Proto-Oncogene Proteins c-akt, Wnt Signaling Pathway

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