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Updated: Jun 18, 2026

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
08:34

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer

Published on: April 13, 2015

Deregulated GSK3{beta} sustains gastrointestinal cancer cells survival by modulating human telomerase reverse

Wei Mai1, Kazuyuki Kawakami, Abbas Shakoori

  • 1Division of Translational and Clinical Oncology, Cancer Research Institute, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|November 12, 2009
PubMed
Abstract

Insights

Dysregulated Glycogen synthase kinase-3beta (GSK3beta) promotes gastrointestinal cancer survival by affecting human telomerase reverse transcriptase (hTERT) and telomerase activity. Inhibiting GSK3beta reduces cancer cell proliferation and increases apoptosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Glycogen synthase kinase-3beta (GSK3beta) is a key regulator in cellular signaling pathways.
  • GSK3beta dysregulation is linked to various diseases including cancer, inflammation, and metabolic disorders.

Purpose of the Study:

  • To investigate the expression, activity, and role of GSK3beta in gastrointestinal, pancreatic, and liver cancers.
  • To determine if GSK3beta inhibition impacts cancer cell survival, proliferation, and apoptosis.

Main Methods:

  • Examined GSK3beta expression and activity in cancer cell lines and patient tissues using Western immunoblotting and kinase assays.
  • Assessed the effects of GSK3beta inhibitors and RNA interference on cancer cells in vitro and in xenografts.
  • Compared the impact of GSK3beta inhibition on human telomerase reverse transcriptase (hTERT) and telomerase activity in cancer cells versus normal cells.

Main Results:

  • Elevated GSK3beta expression, activity, and tyrosine 216 phosphorylation were observed in cancer cells and tissues.
  • GSK3beta inhibition reduced cancer cell survival and proliferation while increasing apoptosis in most cancer models.
  • Inhibition of GSK3beta in colon cancer cells led to decreased hTERT expression and telomerase activity.

Conclusions:

  • Aberrant GSK3beta activity is crucial for sustaining gastrointestinal cancer cell survival.
  • GSK3beta modulates cancer cell fate through the regulation of hTERT and telomerase.

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