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CCAAT/enhancer-binding protein-β functions as a negative regulator of Wnt/β-catenin signaling through activation of

Seoyoung Park1, Mi-Sun Lee2, Jungsug Gwak3

  • 1BK21 PLUS Program, Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul, 02707, Republic of Korea.

Cell Death & Disease
|October 5, 2018
PubMed

Insights

CCAAT/enhancer-binding protein-β (C/EBP-β) activates axis inhibition protein 1 (AXIN1) gene expression, reducing Wnt/β-catenin signaling. This discovery offers a new strategy for developing anticancer drugs targeting this pathway.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Cancer Research

Background:

  • Axin1 is a key negative regulator of the Wnt/β-catenin pathway, primarily controlled by proteasomal degradation.
  • Transcriptional regulation of Axin1 has not been previously elucidated.

Purpose of the Study:

  • To investigate the transcriptional regulation of the axis inhibition protein 1 (AXIN1) gene.
  • To explore the role of CCAAT/enhancer-binding protein-β (C/EBP-β) in regulating Wnt/β-catenin signaling.

Main Methods:

  • Assessed C/EBP-β's interaction with the AXIN1 gene's 5'-upstream regulatory sequences.
  • Utilized Drosophila and zebrafish models for functional analysis.
  • Employed small molecules to modulate C/EBP-β levels in hepatoma cells.

Main Results:

  • Demonstrated that C/EBP-β directly activates AXIN1 gene expression by binding to its cis-regulatory elements.
  • Confirmed C/EBP-β's negative regulation of the Wnt/β-catenin pathway in vivo.
  • Showed that up-regulating C/EBP-β increases AXIN1 expression, decreases intracellular β-catenin, and inhibits hepatoma cell growth.

Conclusions:

  • CCAAT/enhancer-binding protein-β (C/EBP-β) transcriptionally activates AXIN1, providing a novel mechanism for Axin homeostasis.
  • C/EBP-β mediated regulation of AXIN1 offers a potential therapeutic strategy for cancers driven by Wnt/β-catenin signaling.

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