Targeting GSK3 and Associated Signaling Pathways Involved in Cancer

Cells

卷:9

Saverio Candido¹  Massimo Libra¹  StephenL. Abrams²  JamesA. McCubrey²  ShawM. Akula²  LindaS. Steelman²  Agnieszka Gizak³  Dariusz Rakus³  Przemysław Duda³  AlbertoM. Martelli⁴  Lucio Cocco⁴  Stefano Ratti⁴  Giuseppe Montalto⁵  Melchiorre Cervello⁵ 

[1] Department of Biomedical and Biotechnological Sciences—Oncological, Clinical and General Pathology Section, University of Catania, 95131 Catania, Italy;

[2] Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27858 USA;

[3] Department of Molecular Physiology and Neurobiology, University of Wrocław, Sienkiewicza 21, 50-335, Wroclaw, Poland;

[4] Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, 40138 Bologna, Italy;

[5] Institute for Biomedical Research and Innovation, National Research Council (CNR), 128.000 Palermo, Italy;

关键词: GSK-3;    targeted therapy;    natural products;    drug resistance;   

DOI  :  10.3390/cells9051110

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown