Inhibition of GSK3α/β impairs the progression of HNSCC

Lisa Schulz1, Ralph Pries1, Aruna Sree Lanka1

  • 1Department of Otorhinolaryngology, University of Luebeck, Luebeck 23538, Germany.

Oncotarget
|July 3, 2018
PubMed
Abstract

Insights

Glycogen synthase kinase 3 (GSK3) inhibition significantly reduces head and neck squamous cell cancer (HNSCC) growth and migration. Targeting GSK3 offers a promising therapeutic strategy for HNSCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Head and neck squamous cell cancer (HNSCC) is a prevalent malignancy with a critical need for novel therapies.
  • Glycogen synthase kinase 3 (GSK3) has demonstrated varied roles in human cancers, acting as either a tumor suppressor or promoter.
  • Understanding GSK3's specific functions in HNSCC progression is essential for developing targeted treatments.

Purpose of the Study:

  • To investigate the role of glycogen synthase kinase 3 (GSK3) in the progression of head and neck squamous cell cancer (HNSCC).
  • To evaluate the effects of GSK3 inhibition on HNSCC cell viability, migration, and epithelial-mesenchymal transition (EMT).
  • To explore GSK3's influence on inflammatory cytokine expression in HNSCC.

Main Methods:

  • Analysis of baseline expression and activity of GSK3α/β using immunohistochemistry and western blotting.
  • Treatment of HNSCC cell lines with the GSK3α/β inhibitor SB 216763.
  • Assessment of cell viability (MTT assay), migration (xCELLigence), EMT markers (PCR Array), and inflammatory cytokine gene expression (Taqman probes).

Main Results:

  • GSK3α/β inhibition by SB 216763 resulted in dose-dependent reduction in HNSCC cell growth and migration.
  • Inhibition of GSK3α/β led to significant alterations in EMT markers and functional EMT dysregulation.
  • GSK3 differentially mediated the expression of TLR4- and TLR3-induced inflammatory cytokines in HNSCC, independent of NFkB activity.

Conclusions:

  • GSK3α/β is a critical regulator of proliferation and migration in HNSCC progression.
  • GSK3 plays a significant role in various regulatory networks governing HNSCC.
  • GSK3 represents a potential therapeutic target for clinical drug development in HNSCC.
Keywords:
GSK3HNSCC

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