Glycogen synthase kinase 3β in tumorigenesis and oncotherapy (Review)

Oncol Rep. 2020 Dec;44(6):2373-2385. doi: 10.3892/or.2020.7817. Epub 2020 Oct 20.

Abstract

Glycogen synthase kinase 3β (GSK 3β), a multifunctional serine and threonine kinase, plays a critical role in a variety of cellular activities, including signaling transduction, protein and glycogen metabolism, cell proliferation, cell differentiation, and apoptosis. Therefore, aberrant regulation of GSK 3β results in a broad range of human diseases, such as tumors, diabetes, inflammation and neurodegenerative diseases. Accumulating evidence has suggested that GSK 3β is correlated with tumorigenesis and progression. However, GSK 3β is controversial due to its bifacial roles of tumor suppression and activation. In addition, overexpression of GSK 3β is involved in tumor growth, whereas it contributes to the cell sensitivity to chemotherapy. However, the underlying regulatory mechanisms of GSK 3β in tumorigenesis remain obscure and require further in‑depth investigation. In this review, we comprehensively summarize the roles of GSK 3β in tumorigenesis and oncotherapy, and focus on its potentials as an available target in oncotherapy.

Keywords: glycogen synthase kinase 3β; tumorigenesis; oncotherapy; GSK 3β inhibitors.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents, Immunological / pharmacology
  • Antineoplastic Agents, Immunological / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Apoptosis / drug effects
  • Carcinogenesis / drug effects
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology*
  • Disease Models, Animal
  • Disease Progression
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / immunology
  • Glycogen Synthase Kinase 3 beta / antagonists & inhibitors
  • Glycogen Synthase Kinase 3 beta / metabolism*
  • Humans
  • Lymphocytes / drug effects
  • Lymphocytes / enzymology
  • Lymphocytes / immunology
  • Mice
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / pathology*
  • Phosphorylation / drug effects
  • Phosphorylation / genetics
  • Phosphorylation / immunology
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Proteolysis / drug effects
  • Signal Transduction / drug effects
  • Transcription Factors / metabolism*

Substances

  • Antineoplastic Agents, Immunological
  • Protein Kinase Inhibitors
  • Transcription Factors
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, mouse