Glycogen synthase kinase 3 in Wnt signaling pathway and cancer

IUBMB Life. 2015 Dec;67(12):914-22. doi: 10.1002/iub.1454. Epub 2015 Nov 24.

Abstract

Glycogen synthase kinase 3 (GSK-3) was first discovered in 1980 as one of the key enzymes of glycogen metabolism. Since then, GSK-3 has been revealed as one of the master regulators of a diverse range of signaling pathways, including those activated by Wnts, participating in the regulation of numerous cellular functions, suggesting that its activity is tightly regulated. Numerous studies have pointed to an association of GSK-3 dysregulation with the onset and progression of human diseases, including diabetes mellitus, obesity, inflammation, neurological illnesses, and cancer. Therefore, GSK-3 is recognized as an attractive therapeutic target in multiple disorders. However, the great number of substrates that are phosphorylated by GSK-3 has raised the question of whether this limits its feasibility as a therapeutic target because of the potential disruption of many cellular processes and also by the fear that inhibition of GSK-3 may stimulate or aid in malignant transformation, as GSK-3 can phosphorylate pro-oncogenic factors. This mini review focuses on the role played by GSK-3 in Wnt signaling pathway and cancer using as model colon cancer.

Keywords: GSK-3; GSK-3 regulation; Wnt signaling; colon cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / metabolism*
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors
  • Glycogen Synthase Kinase 3 / genetics
  • Glycogen Synthase Kinase 3 / metabolism*
  • Humans
  • Isoenzymes / metabolism
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Protein Kinase Inhibitors / pharmacology
  • Protein Processing, Post-Translational
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway*

Substances

  • Isoenzymes
  • Protein Kinase Inhibitors
  • Wnt Proteins
  • Glycogen Synthase Kinase 3