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Updated: Nov 19, 2025

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Kinase GSK3β functions as a suppressor in colorectal carcinoma through the FTO-mediated MZF1/c-Myc axis

Zeyan Zhang1, Qianfu Gao1, Shanchao Wang1

  • 1Anorectal Department, Linyi People' s Hospital, Linyi, China.

Journal of Cellular and Molecular Medicine
|February 3, 2021
PubMed

Insights

Glycogen synthase kinase 3 beta (GSK3β) suppresses colorectal cancer (CRC) progression by targeting the FTO/MZF1/c-Myc pathway. This study reveals GSK3β as a potential therapeutic target for CRC by elucidating its molecular mechanisms.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Colorectal carcinoma (CRC) presents a significant global health challenge with limited efficacy of current biomarkers.
  • Glycogen synthase kinase 3 beta (GSK3β) is identified as a potential therapeutic target in CRC, but its precise molecular functions remain unclear.

Purpose of the Study:

  • To investigate the regulatory role of GSK3β in colorectal cancer progression.
  • To elucidate the molecular mechanisms involving the FTO/MZF1/c-Myc axis in GSK3β-mediated CRC regulation.

Main Methods:

  • Analysis of GSK3β, FTO, MZF1, and c-Myc expression in CRC samples.
  • In vitro experiments using transfection of plasmids to assess GSK3β's effect on CRC cell functions.
  • Assessment of FTO protein stability, MZF1 m6A modification, and FTO-MZF1 interaction.
  • In vivo studies to validate GSK3β's role in CRC growth.

Main Results:

  • Lower GSK3β expression and higher FTO, MZF1, and c-Myc expression were observed in CRC.
  • GSK3β reduces FTO protein stability via ubiquitination and inhibits MZF1 expression through FTO-regulated m6A modification.
  • GSK3β suppresses c-Myc expression, thereby hindering CRC cell proliferation and in vivo tumor growth.
  • Overexpression of c-Myc reversed the inhibitory effect of GSK3β on CRC growth in vivo.

Conclusions:

  • GSK3β acts as a tumor suppressor in colorectal cancer.
  • The findings highlight the GSK3β/FTO/MZF1/c-Myc pathway as a novel mechanism regulating CRC progression.
  • GSK3β represents a promising therapeutic target for colorectal cancer treatment.
Keywords:
N6-methyladenosinecolorectal carcinomafat mass and obesity-associated proteinglycogen synthase kinase 3 betamyeloid zinc finger 1

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