Colorectal cancer remains the second leading cause of cancer-related deaths worldwide, highlighting the urgent need for more effective therapies and a deeper understanding of its molecular basis. Drug repurposing has gained traction as a viable strategy to target dysregulated oncogenic pathways. Statins, commonly prescribed for lowering cholesterol, have recently shown potential anti-cancer effects. In this study, we explore how statin treatment influences lipid metabolism, gene expression, and proteomic profiles in colorectal cancer models. Our findings provide direct evidence that statins selectively modulate key components of the Wnt/β-catenin signaling pathway, a major driver of adenoma formation, including members of the special AT-rich sequence-binding (SATB) protein family. We show that statin treatment downregulates SATB1, a known promoter of tumorigenesis in the context of Wnt activation, while simultaneously upregulating SATB2, which plays an opposing role. This reciprocal regulation shifts cellular phenotypes between epithelial and mesenchymal states in 3D spheroid models. Together, these results highlight the therapeutic potential of statins in colorectal cancer and support their consideration in drug repurposing approaches.
Keywords: SATB1; Wnt/β-catenin signaling; colorectal cancer; statins; tumor-suppressive phenotype.