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Statins exhibit anti-tumor potential by modulating Wnt/β-catenin signaling in colorectal cancer

Sneha Tripathi1, Ekta Gupta1,2, Rutika Naik1

  • 1Laboratory of Chromatin Biology and Epigenetics, Indian Institute of Science Education and Research, Pune 411008, India.

Oncotarget
|July 21, 2025
PubMed

Insights

Statins show promise for colorectal cancer treatment by altering lipid metabolism and gene expression. They selectively modulate the Wnt/β-catenin pathway, downregulating SATB1 and upregulating SATB2, offering a potential drug repurposing strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Colorectal cancer is a leading cause of global cancer deaths, necessitating novel therapeutic strategies.
  • Drug repurposing, particularly using statins, is an emerging approach to target cancer pathways.
  • Statins, cholesterol-lowering drugs, exhibit potential anti-cancer properties.

Purpose of the Study:

  • To investigate the effects of statin treatment on colorectal cancer models.
  • To elucidate how statins influence lipid metabolism, gene expression, and proteomic profiles.
  • To determine the impact of statins on the Wnt/β-catenin signaling pathway and SATB protein family.

Main Methods:

  • Utilized colorectal cancer models to assess statin treatment effects.
  • Analyzed changes in lipid metabolism, gene expression, and proteomic profiles.
  • Investigated the modulation of the Wnt/β-catenin pathway and SATB1/SATB2 expression in 3D spheroid models.

Main Results:

  • Statin treatment selectively modulated key components of the Wnt/β-catenin signaling pathway.
  • Statin administration downregulated SATB1 (tumorigenesis promoter) and upregulated SATB2.
  • Reciprocal regulation of SATB1/SATB2 by statins induced shifts in cellular phenotypes between epithelial and mesenchymal states.

Conclusions:

  • Statins demonstrate therapeutic potential in colorectal cancer by targeting the Wnt/β-catenin pathway.
  • The observed reciprocal regulation of SATB1 and SATB2 by statins offers a novel mechanism for cancer therapy.
  • Statin repurposing should be considered for colorectal cancer treatment strategies.
Keywords:
SATB1Wnt/β-catenin signalingcolorectal cancerstatinstumor-suppressive phenotype

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